WO1999016417A1 - Buccal, polar and non-polar spray or capsule - Google Patents

Buccal, polar and non-polar spray or capsule Download PDF

Info

Publication number
WO1999016417A1
WO1999016417A1 PCT/US1997/017899 US9717899W WO9916417A1 WO 1999016417 A1 WO1999016417 A1 WO 1999016417A1 US 9717899 W US9717899 W US 9717899W WO 9916417 A1 WO9916417 A1 WO 9916417A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
active compound
polar solvent
flavoring agent
capsule
Prior art date
Application number
PCT/US1997/017899
Other languages
French (fr)
Inventor
Harry A. Dugger, Iii
Original Assignee
Flemington Pharmaceutical Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Flemington Pharmaceutical Corporation filed Critical Flemington Pharmaceutical Corporation
Priority to EP07023005A priority Critical patent/EP1952802A3/en
Priority to PCT/US1997/017899 priority patent/WO1999016417A1/en
Priority to EP00109347A priority patent/EP1029536B1/en
Priority to EP97911621A priority patent/EP1019019A1/en
Priority to ES00109347T priority patent/ES2293875T3/en
Priority to DE69738333T priority patent/DE69738333T2/en
Priority to CA2306024A priority patent/CA2306024C/en
Priority to JP2000513555A priority patent/JP2001517689A/en
Priority to EP00109357A priority patent/EP1036561A1/en
Priority to AU48946/97A priority patent/AU4894697A/en
Priority to EP20080020267 priority patent/EP2042161A1/en
Publication of WO1999016417A1 publication Critical patent/WO1999016417A1/en
Priority to US10/100,156 priority patent/US6676931B2/en
Priority to US10/230,085 priority patent/US20030095926A1/en
Priority to US10/230,060 priority patent/US20030077227A1/en
Priority to US10/230,080 priority patent/US20030082107A1/en
Priority to US10/230,072 priority patent/US20030190286A1/en
Priority to US10/230,073 priority patent/US20030077228A1/en
Priority to US10/230,084 priority patent/US20030095925A1/en
Priority to US10/230,059 priority patent/US20030185761A1/en
Priority to US10/230,086 priority patent/US20030095927A1/en
Priority to US10/230,075 priority patent/US20030077229A1/en
Priority to US10/327,195 priority patent/US6998110B2/en
Priority to US10/663,817 priority patent/US20040062716A1/en
Priority to US10/671,710 priority patent/US20040136913A1/en
Priority to US10/671,719 priority patent/US20040136915A1/en
Priority to US10/671,720 priority patent/US20040141923A1/en
Priority to US10/671,709 priority patent/US20050163719A1/en
Priority to US10/671,708 priority patent/US20050180923A1/en
Priority to US10/671,717 priority patent/US20040136914A1/en
Priority to US10/671,715 priority patent/US7632517B2/en
Priority to US10/726,625 priority patent/US6969508B2/en
Priority to US10/726,585 priority patent/US6977070B2/en
Priority to US10/834,815 priority patent/US20050002867A1/en
Priority to US10/928,989 priority patent/US20050025714A1/en
Priority to US10/928,952 priority patent/US20050025712A1/en
Priority to US10/928,997 priority patent/US20050025717A1/en
Priority to US10/928,995 priority patent/US20050025715A1/en
Priority to US10/928,979 priority patent/US20050025713A1/en
Priority to US10/929,001 priority patent/US20050142069A1/en
Priority to US10/928,996 priority patent/US20050025716A1/en
Priority to US11/211,488 priority patent/US20050281752A1/en
Priority to US11/211,487 priority patent/US20050287075A1/en
Priority to US11/211,549 priority patent/US20050281753A1/en
Priority to US11/366,663 priority patent/US20060165604A1/en
Priority to US11/384,444 priority patent/US20060159624A1/en
Priority to US11/391,297 priority patent/US20060171896A1/en
Priority to US11/429,953 priority patent/US20060198790A1/en
Priority to US11/440,095 priority patent/US20060210484A1/en
Priority to US11/442,137 priority patent/US20060222597A1/en
Priority to US11/443,253 priority patent/US20060216240A1/en
Priority to US11/443,254 priority patent/US20060216241A1/en
Priority to US11/443,260 priority patent/US20070048229A1/en
Priority to US11/929,368 priority patent/US20080170995A1/en
Priority to US12/350,602 priority patent/US20090162297A1/en
Priority to US12/350,898 priority patent/US20090118170A1/en
Priority to US12/350,915 priority patent/US20090131514A1/en
Priority to US12/351,275 priority patent/US20090186099A1/en
Priority to US12/351,179 priority patent/US20090186035A1/en
Priority to US12/351,606 priority patent/US20090124554A1/en
Priority to US12/351,576 priority patent/US20090162298A1/en
Priority to US12/351,490 priority patent/US20090123387A1/en
Priority to US12/394,903 priority patent/US20090162300A1/en
Priority to US12/576,457 priority patent/US8236285B2/en
Priority to US12/632,719 priority patent/US20100152262A1/en
Priority to US12/692,213 priority patent/US20100209541A1/en
Priority to US13/197,207 priority patent/US20120027879A1/en
Priority to US13/208,429 priority patent/US20110293536A1/en
Priority to US13/445,331 priority patent/US9078816B2/en
Priority to US13/450,987 priority patent/US20120202866A1/en
Priority to US13/467,441 priority patent/US20120252846A1/en
Priority to US13/683,530 priority patent/US20130199519A1/en
Priority to US14/218,518 priority patent/US20140200516A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A61K38/13—Cyclosporins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A61K9/124—Aerosols; Foams characterised by the propellant

Definitions

  • Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. P. 3, 1 55,574, Silson et aj., U.S. P. 5,01 1 ,678, Wang et aj., and by Parnell in U.S. P. 5, 1 28, 1 32. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered.
  • SUMMARY OF THE INVENTION A buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect.
  • compositions of the present invention for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable non-polar solvent comprising in weight % of total composition: pharmaceutically acceptable propellant 5-80%, non- polar solvent 20-85 %, active compound 0.05-50%, suitably additionally comprising, by weight of total composition a flavoring agent 0.01 -10%.
  • the composition comprises: propellant 1 0-85 %, non-polar solvent 25-89.9%, active compound 0.01 -40%, flavoring agent 1 -8%; most suitably propellant 20-70%, non-polar solvent 30-74.75 %, active compound 0.25-35 %, flavoring agent 2-7.5 %.
  • compositions of the present invention for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent comprising in we ⁇ ght% of total composition: polar solvent 30-99.69%, active compound 0.001 -60%, suitably additionally comprising, by weight of total composition a flavoring agent 0.1 -10%.
  • the composition comprises: polar solvent 37- 98.58%, active compound 0.005-55 %, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01 -40%, flavoring agent 0.75-7.5%.
  • the soft bite gelatin capsule comprises: non-polar solvent 21 .5-99.975 %, emulsifier 0-1 5%, active compound 0.025-70%, flavoring agent 1 -8%; most suitably: non- polar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1 -65.0%, flavoring agent 2-6%.
  • the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0- 1 5 %, active compound 0.025-55 %, flavoring agent 1 -8%; most suitably: polar solvent 44-96.925 %, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%
  • the buccal pump spray composition of the present invention for transmucosal administration of a pharmacologically active compound where said active compound is soluble in a pharmacologically acceptable non-polar solvent said composition comprise in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55 %, flavoring agent 0.1 -10%.
  • a further object is a sealed aerosol spray container containing a composition of the non polar spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
  • the propellant is a non-Freon material, preferably a C 3 . 8 hydrocarbon of a linear or branched configuration.
  • the propellant should be substantially non-aqueous.
  • the propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.
  • the non-polar solvent is a non-polar hydrocarbon, preferably a C 7 . 18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol.
  • the solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at 0-40 ° C at a pressure range of 1 -3 atm.
  • the non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, will does not allow entry of atmospheric gasses with each activation.
  • Such containers are commercially available.
  • a further object is a pump spray container containing a composition of the spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
  • a further object is a soft gelatin bite capsule containing a composition of as set forth above.
  • the formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.)
  • the polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound
  • the solvent preferably dissolves the active compound.
  • other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill.
  • Soft gelatin capsules are well known in the art. See, for example, U.S. P. 4,935,243, Borkan et al., which is incorporated herein by reference for its teaching of such capsules.
  • the capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds.
  • the shell of a soft gelatin capsule of the invention may comprise, for example: gelatine 50-75 %, glycerine 20-30%, colorants 0.5- 1 .5 %, water 5-10%, and sorbitol 2- 10% .
  • the active compound may include biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals.
  • the active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application
  • FIG. 1 is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.
  • the preferred active compounds of the present invention are in anionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or spray compositions, they are soluble in the spray solvent) . These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) First pass effect.
  • propellants for the non polar sprays propane, N-butane, iso- butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used.
  • N-butane and iso-butane, as single gases, are the preferred propellants.
  • the propellant it is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1 -0.2%. (All percentages herein are by weight unless otherwise indicated .)
  • the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The con- centration of each of these should be less than 0.1 %, except that water may be as high as 0.2% .
  • Suitable non-polar solvents for the capsules and the non-polar sprays include (C 2 -C 24 ) fatty acid C 2 -C 6 esters, C 7 -C 18 hydrocarbon, C 2 -C 6 alkanoyl esters, and the triglycerides of the corresponding acids.
  • other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.
  • solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C 2 -C 8 ) mono-and polyols and alcohols of C 7 -C 18 linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • PEG polyethyleneglycols
  • C 2 -C 8 low molecular weight mono-and polyols and alcohols of C 7 -C 18 linear or branch chain hydrocarbons
  • glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
  • the preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc. ), and combinations thereof.
  • the active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, Octreotide acetate, cal- citonin-salmon, insulin lispro, sumat ⁇ ptan succmate, clozepine, cyclo- benzap ⁇ ne, dexfenfluramine hydrochlo ⁇ de, glybu ⁇ de, zidovudine, erythro- mycin, ciprofloxac ⁇ n, ondansetron hydrochlor ⁇ de, dimenhydr ⁇ nate, c ⁇ metidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thro- methamine, carboprost, carnitine, valerian, echinacea, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate
  • compositions of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof.
  • pharmaceutically acceptable salts refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases.
  • salts may be prepared from pharmaceutically acceptable non-toxic bases.
  • Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts.
  • Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion- exchange resins such as arginine, betaine, caffeine, choline, N,N'- dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl- aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethyl- piperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl- glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc.
  • basic ion- exchange resins such as arginine, betaine, caffeine, choline
  • salts may be prepared from pharmaceutically acceptable non-toxic acids.
  • acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane- sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, panto- thenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc.
  • Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids.
  • Amounts preferred amount most preferred amount insulin 20-60 4-55 5-50 glycerin, 0.1-10 0.25-5 0.1-1.5 dibasic sodium phosphate, 1-15 2.5-10 4-8 m-cresol, 1-25 5-25 7.5-12.5 zinc oxide 0.01-0.25 .05-0.15 0.075-0.10 m-cresol, 0.1-1 0.2-0.8 0.4-0.6 phenol ' trace amounts trace amounts trace amounts ethanol 5-20 7.5-15 9-12 water 30-90 40-80 50-75 propylene glycol 5-20 7.5-15 9-12 flavors 0.1-5 0.5-3 0.75-2 adjust pH to 7.0-7.8 with HCI or NaOH EXAMPLE 2
  • CIMS active amines and their salts including but not limited to tricyclic amines, GABA analogues, thiazides, phenothiazine derivatives, Serotonin antagonists and serotonin reuptake inhibitors
  • Amounts preferred amount most preferred amount sumatriptan succinate 0.5-30 1 -20 10-1 5 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-1 5 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 10-15 flavors 0.1 -5 1 -4 2-3
  • Clozepine 0.5-30 1 -20 10-1 5 ethanol 5-60 7.5-50 1 0-20 propylene glycol 5-30 7.5-20 ' 1 0-1 5 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 1 0-1 5 flavors 0.1 -5 1 -4 2-3 D.
  • ClozeDine Non-Polar lingual spray with propellant 0.5-30 1 -20 10-1 5 ethanol 5-60 7.5-50 1 0-20 propylene glycol 5-30 7.5-20 ' 1 0-1 5 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 1 0-1 5 flavors 0.1 -5 1 -4 2-3 D.
  • Glyburide 0.01-10 0.025-7.5 0.1-4 olive oil 30-60 35-55 30-50 polyoxyethyl- 30-60 35-55 30-50 ated oleic glyce ⁇ des flavors 01-5 1-4 2-3
  • Erythromycin 25-65 30-50 35-45 polyoxyethylene glycol 5-70 30-60 45-55 glycerin 5-20 7.5-15 10-12.5 flavors 1-10 2-8 3-6
  • Ciprofloxacin hydrochloride 25-65 35-55 40-50 glycerin 5-20 7.5-15 10-12.5 polyethylene glycol 20-75 30-65 40-60 flavors 1-10 2-8 3-6
  • Dimenhydrinate 0.5-30 2-25 3-15 glycerin 5-20 7.5-15 10-12.5 polyethylene glycol 45-95 50-90 55-85 flavors 1-10 2-8 3-6
  • Ph is adjusted with sodium hydroxide and/or hydrochloric acid
  • Echinacea extract 30-85 40-75 45-55 soya oil 7550 10-40 125-35 soya lecithin 0001 1 0 0005-05 01-01

Abstract

Buccal aerosol sprays or capsule using polar and non-polar solvent have now been developed which provide biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect. The buccal polar compositions of the invention comprises formulation (I): aqueous polar solvent 30-99.89 %, active compound 0.001-60 %, optionally containing flavoring agent 0.1-10 %. The non-polar composition of the invention comprises formulation (II): non-polar solvent 20-85 %, active compound 0.005-50 %, and optionally flavoring agent 0.1-10 % and propellant 50-80 %.

Description

TITLE OF THE INVENTION BUCCAL, POLAR AND NON-POLAR SPRAY OR CAPSULE
BACKGROUND OF THE INVENTION It is known that certain biologically active compounds are better absorbed through the oral mucosa than through other routes of administration, such as through the stomach or intestine. However, formulations suitable for such administration by these latter routes present their own problems. For example, the biologically active compound must be compatible with the other components of the composition such as propellants, solvents, etc. Many such formulations have been proposed. For example, U.S. P. 4, 689,233, Dvorsky et aj., describes a soft gelatin capsule for the administration of the anti-coronary drug nifedipine dissolved in a mixture of polyether alcohols. U.S. P. 4,755,389, Jones et a|., describes a hard gelatin chewable capsule containing nifedipine. A chewable gelatin capsule containing a solution or dispersion of a drug is described in U.S. P. 4,935,243, Borkan et aj. U.S. P. 4,91 9,91 9, Aouda et aj, and U.S. P. 5,370,862, Klokkers-Bethke, describe a nitroglycerin spray for administration to the oral mucosa comprising nitroglycerin, ethanol, and other components. An orally administered pump spray is described by Cholcha in U.S. P. 5, 186,925. Aerosol compositions containing a hydrocarbon propellant and a drug for administration to a mucosal surface are described in U.K. 2,082,457, Su, U.S. P. 3, 1 55,574, Silson et aj., U.S. P. 5,01 1 ,678, Wang et aj., and by Parnell in U.S. P. 5, 1 28, 1 32. It should be noted that these references discuss bioavailability of solutions by inhalation rather than through the membranes to which they are administered. SUMMARY OF THE INVENTION A buccal aerosol spray or soft bite gelatin capsule using a polar or non-polar solvent has now been developed which provides biologically active compounds for rapid absorption through the oral mucosa, resulting in fast onset of effect.
The buccal aerosol spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable non-polar solvent comprising in weight % of total composition: pharmaceutically acceptable propellant 5-80%, non- polar solvent 20-85 %, active compound 0.05-50%, suitably additionally comprising, by weight of total composition a flavoring agent 0.01 -10%. Preferably the composition comprises: propellant 1 0-85 %, non-polar solvent 25-89.9%, active compound 0.01 -40%, flavoring agent 1 -8%; most suitably propellant 20-70%, non-polar solvent 30-74.75 %, active compound 0.25-35 %, flavoring agent 2-7.5 %.
The buccal polar spray compositions of the present invention, for transmucosal administration of a pharmacologically active compound soluble in a pharmacologically acceptable polar solvent comprising in weιght% of total composition: polar solvent 30-99.69%, active compound 0.001 -60%, suitably additionally comprising, by weight of total composition a flavoring agent 0.1 -10%. Preferably the composition comprises: polar solvent 37- 98.58%, active compound 0.005-55 %, flavoring agent 0.5-8%; most suitably polar solvent 60.9-97.06%, active compound 0.01 -40%, flavoring agent 0.75-7.5%.
The soft bite gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable non-polar solvent, having charged thereto a fill composition comprising in weight % of total composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01 -80%, provided that said fill composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 0.01 -10%. Preferably, the soft bite gelatin capsule comprises: non-polar solvent 21 .5-99.975 %, emulsifier 0-1 5%, active compound 0.025-70%, flavoring agent 1 -8%; most suitably: non- polar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1 -65.0%, flavoring agent 2-6%.
The soft bite polar gelatin capsules of the present invention for transmucosal administration of a pharmacologically active compound, at least partially soluble in a pharmacologically acceptable polar solvent, having charged thereto a composition comprising in weight % of total composition: polar solvent 25-99.89%, emulsifier 0-20%, active compound 0.01 -65%, provided that said composition contains less than 10% of water, suitably additionally comprising, by weight of the composition: flavoring agent 01 -10%. Preferably, the soft bite gelatin capsule comprises: polar solvent 37-99.95%, emulsifier 0- 1 5 %, active compound 0.025-55 %, flavoring agent 1 -8%; most suitably: polar solvent 44-96.925 %, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%
The buccal pump spray composition of the present invention for transmucosal administration of a pharmacologically active compound where said active compound is soluble in a pharmacologically acceptable non-polar solvent said composition comprise in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55 %, flavoring agent 0.1 -10%.
It is an object of the invention to coat the mucosal membranes either with extremely fine droplets of spray containing the active compounds or a solution or paste thereof from bite capsules. It is also an object of the invention to administer to a mammalian in need of same preferably man, a predetermined amount of a biologically active compound by this method or from a soft gelatin bite capsule.
A further object is a sealed aerosol spray container containing a composition of the non polar spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
As the propellant evaporates after activation of the aerosol valve, a mist of fine droplets is formed which contains solvent and active compound .
The propellant is a non-Freon material, preferably a C3. 8 hydrocarbon of a linear or branched configuration. The propellant should be substantially non-aqueous. The propellant produces a pressure in the aerosol container such that under expected normal usage it will produce sufficient pressure to expel the solvent from the container when the valve is activated but not excessive pressure such as to damage the container or valve seals.
The non-polar solvent is a non-polar hydrocarbon, preferably a C7.18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as miglyol. The solvent must dissolve the active compound and be miscible with the propellant, i.e., solvent and propellant must form a single phase at 0-40 ° C at a pressure range of 1 -3 atm.
The non-polar aerosol spray compositions of the invention are intended to be administered from a sealed, pressurized container. Unlike a pump spray, which allows the entry of air into the container after every activation, the aerosol container of the invention is sealed at the time of manufacture. The contents of the container are released by activation of a metered valve, will does not allow entry of atmospheric gasses with each activation. Such containers are commercially available.
A further object is a pump spray container containing a composition of the spray formulation, and a metered valve suitable for releasing from said container a predetermined amount of said composition.
A further object is a soft gelatin bite capsule containing a composition of as set forth above. The formulation may be in the form of a viscous solution or paste containing the active compounds. Although solutions are preferred, paste fills may also be used where the active compound is not soluble or only partially soluble in the solvent of choice. Where water is used to form part of the paste composition, it should not exceed 10% thereof. (All percentages herein are by weight unless otherwise indicated.)
The polar or non-polar solvent is chosen such that it is compatible with the gelatin shell and the active compound The solvent preferably dissolves the active compound. However, other components wherein the active compound is not soluble or only slightly soluble may be used and will form a paste fill.
Soft gelatin capsules are well known in the art. See, for example, U.S. P. 4,935,243, Borkan et al., which is incorporated herein by reference for its teaching of such capsules. The capsules of the present invention are intended to be bitten into to release the low viscosity solution or paste therein, which will then coat the buccal mucosa with the active compounds. Typical capsules, which are swallowed whole or bitten and then swallowed, deliver the active compounds the stomach, which results in significant lag time before maximum blood levels can be achieved or subject the compound to a large first pass effect. Because of the enhanced absorption of the compounds through the oral mucosa and no chance of a first pass effect, use of the bite capsules of the invention will eliminate much of the lag time, resulting in hastened onset of biological effect. The shell of a soft gelatin capsule of the invention may comprise, for example: gelatine 50-75 %, glycerine 20-30%, colorants 0.5- 1 .5 %, water 5-10%, and sorbitol 2- 10% .
The active compound may include biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostaglandins and neutraceuticals.
The active compounds may also include antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics. While not limited thereto, these active compounds are particularly suitable for non-polar pump spray formulation and application
BRIEF DESCRIPTION OF THE DRAWING The figure is a schematic diagram showing routes of absorption and processing of pharmacologically active substances in a mammalian system.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The preferred active compounds of the present invention are in anionized, salt form or as the free base of the pharmaceutically acceptable salts thereof (provided, for the aerosol or spray compositions, they are soluble in the spray solvent) . These compounds are soluble in the non-polar solvents of the invention at useful concentrations or can be prepared as pastes at useful concentrations. These concentrations may be less than the standard accepted dose for these compounds since there is enhanced absorption of the compounds through the oral mucosa. This aspect of the invention is especially important when there is a large (40-99.99%) First pass effect. As propellants for the non polar sprays, propane, N-butane, iso- butane, N-pentane, iso-pentane, and neo-pentane, and mixtures thereof may be used. N-butane and iso-butane, as single gases, are the preferred propellants. It is permissible for the propellant to have a water content of no more than 0.2%, typically 0.1 -0.2%. (All percentages herein are by weight unless otherwise indicated .) It is also preferable that the propellant be synthetically produced to minimize the presence of contaminants which are harmful to the active compounds. These contaminants include oxidizing agents, reducing agents, Lewis acids or bases, and water. The con- centration of each of these should be less than 0.1 %, except that water may be as high as 0.2% .
Suitable non-polar solvents for the capsules and the non-polar sprays include (C2-C24) fatty acid C2-C6 esters, C7-C18 hydrocarbon, C2-C6 alkanoyl esters, and the triglycerides of the corresponding acids. When the capsule fill is a paste, other liquid components may be used instead of the above low molecular weight solvents. These include soya oil, corn oil, other vegetable oils.
As solvents for the polar capsules or sprays there may be used low molecular weight polyethyleneglycols (PEG) of 400-1000 Mw (preferably 400-600), low molecular weight (C2-C8) mono-and polyols and alcohols of C7-C18linear or branch chain hydrocarbons, glycerin may also be present and water may also be used in the sprays, but only in limited amount in the capsules.
It is expected that some glycerin and water used to make the gelatin shell will migrate from the shell to the fill during the curing of the shell.
Likewise, there may be some migration of components from the fill to the shell during curing and even throughout the shelf-life of the capsule.
Therefore, the values given herein are for the compositions as prepared, it being within the scope of the invention that minor variations will occur.
The preferred flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners (sugars, aspartame, saccharin, etc. ), and combinations thereof.
The active substances include the active compounds selected from the group consisting of cyclosporine, sermorelin, Octreotide acetate, cal- citonin-salmon, insulin lispro, sumatπptan succmate, clozepine, cyclo- benzapπne, dexfenfluramine hydrochloπde, glybuπde, zidovudine, erythro- mycin, ciprofloxacιn, ondansetron hydrochlorιde, dimenhydrιnate, cιmetidine hydrochloride, famotidine, phenytoin sodium, phenytoin, carboprost thro- methamine, carboprost, carnitine, valerian, echinacea, diphenhydramine hydrochloride, isoproterenol hydrochloride, terbutaline sulfate, terbutaline, theophylline, albuterol sulfate, and the like.
The formulations of the present invention comprise an active compound or a pharmaceutically acceptable salt thereof. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic acids or bases including organic and inorganic acids or bases.
When an active compound of the present invention is acidic, salts may be prepared from pharmaceutically acceptable non-toxic bases. Salts derived from all stable forms of inorganic bases include aluminum, ammonium, calcium, copper, iron, lithium, magnesium, manganese, potassium, sodium, zinc, etc. Particularly preferred are the ammonium, calcium, magnesium, potassium, and sodium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion- exchange resins such as arginine, betaine, caffeine, choline, N,N'- dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethyl- aminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethyl- piperidine, glucamine, glucosamine, histidine, isopropylamine, lysine, methyl- glucosamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, theobromine, triethylamine, trimethylamine, tripropylamine, etc.
When an active compound of the present invention is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethane- sulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, mandelic, methanesulfonic, mucic, nitric, pamoic, panto- thenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, etc. Particularly preferred are citric, hydrobromic, maleic, phosphoric, sulfuric, and tartaric acids.
In the discussion of methods of treatment herein, reference to the active compounds is meant to also include the pharmaceutically acceptable salts thereof. While certain formulations are set forth herein, the actual amounts to be administered to the mammal or man in need of same are to be determined by the treating physician.
The invention is further defined by reference to the following examples, which are intended to be illustrative and not limiting. NOT FURNISHED UPON FILING
NOT FURNISHED UPON FILING
Octreotide acetate (Sandostatinw) lingual spray
Amounts preferred amount most preferred amount octreotide acetate 0.001- ■0.5 0.005-0.250 0.01-0.10 acetic acid 1-10 2-8 4-6 sodium acetate 1-10 2-8 4-6 sodium chloride 3-30 5-25 15-20 flavors 0.1-5 0.5-.4 2-3 ethanol 5-30 7.5-20 9.5-15 water 15-95 35-90 65-85 flavors 0.1-5 1-4 2-3
G. Calcitonin-salmon lingual spray
Amounts preferred amount most preferred amount
Calcitonin-salmon 0.001-5 0.005-2 .01-1.5 ethanol 2-15 3-10 7-9.5 water 30-95 50-90 60-80 polyethylene glycol 2-15 3-10 7-9.5 sodium chloride 2.5-20 5-15 10-12.5 flavors 0.1-5 1-4 2-3
insulin lispro. lingual spray
Amounts preferred amount most preferred amount insulin, 20-60 4-55 5-50 glycerin, 0.1-10 0.25-5 0.1-1.5 dibasic sodium phosphate, 1-15 2.5-10 4-8 m-cresol, 1-25 5-25 7.5-12.5 zinc oxide 0.01-0.25 .05-0.15 0.075-0.10 m-cresol, 0.1-1 0.2-0.8 0.4-0.6 phenol ' trace amounts trace amounts trace amounts ethanol 5-20 7.5-15 9-12 water 30-90 40-80 50-75 propylene glycol 5-20 7.5-15 9-12 flavors 0.1-5 0.5-3 0.75-2 adjust pH to 7.0-7.8 with HCI or NaOH EXAMPLE 2
CIMS active amines and their salts: including but not limited to tricyclic amines, GABA analogues, thiazides, phenothiazine derivatives, Serotonin antagonists and serotonin reuptake inhibitors
A. Sumatriptan succinate lingual spray
Amounts preferred amount most preferred amount sumatriptan succinate 0.5-30 1 -20 10-1 5 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-1 5 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 10-15 flavors 0.1 -5 1 -4 2-3
Sumatriptan succinate bite capsule
Amounts preferred amount most preferred amount sumatriptan succinate 0.01 -5 0.05-3.5 0.075-1 .75 polyethylene glycol 25-70 30-60 35-50 glycerin 25-70 30-60 35-50 flavors 0.1 - 1 0 1 -8 3-6
C. Clozepine lingual spray
Amounts preferred amount most preferred amount
Clozepine 0.5-30 1 -20 10-1 5 ethanol 5-60 7.5-50 1 0-20 propylene glycol 5-30 7.5-20 ' 1 0-1 5 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 1 0-1 5 flavors 0.1 -5 1 -4 2-3 D. ClozeDine Non-Polar lingual spray with propellant
Amounts preferred most preferred amount amount
Clozepine 0.5-30 1-20 10-15
Migylol 20-85 25-70 30-40
Butane 15-80 30-75 60-70 flavors 0.1-5 1-4 2-3
E. ClozeDine Non -Polar lingual spray without propellant
Amounts preferred most preferred amount amount
Clozepine 0.5-30 1-20 10-15
Migylol 70-99.5 80-99 85-90 flavors 0.1-5 1-4 2-3
F. CvclobenzaDrine Non polar lingual spray
Amounts preferred most preferred amount amount
Cyclobenzaprine 0.5-30 1-20 10-15
(base)
Migylol 20-85 25-70 30-40
Iso-butane 15-80 30-75 60-70 flavors 0.1-5 1-4 2-3
G. dexfenfluramine hydrochloride lingual spray
Amounts preferred most preferrec amount amount dexfenfluramine Hcl 5-30 7.5-20 10-15 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-15 polyethylene glycol 0-60 30-45 35-40 water 5-30 7.5-20 10-15 flavors 0.1-5 1-4 2-3 EXAMPLE 3
Sulfonylureas
A. Glvburide linqual ε ;pray
Amounts preferred amount most preferred amount
Glyburide 025-25 05-20 0.75-15 ethanol 5-60 7.5-50 10-20 propylene glycol 5-30 7.5-20 10-15 polyethylene glycol 0-60 30-45 35-40 water 2.5-30 5-20 6-15 flavors 01-5 1-4 2-3
B. Glyburide non-pol ar bite capsule
Amounts preferred most preferred amount amount
Glyburide 0.01-10 0.025-7.5 0.1-4 olive oil 30-60 35-55 30-50 polyoxyethyl- 30-60 35-55 30-50 ated oleic glyceπdes flavors 01-5 1-4 2-3
EXAMPLE 4 Antibiotics anti-fungals and anti-virals zidovudine [formerly called azidothymidine (AZT) (Retrovir) non-polar lingual spray
Amounts preferred most preferred amount amount zidovudine 10-50 15-40 25-35
Soya oil 20-85 25-70 30-40
Butane 15-80 30-75 60-70 flavors 0.1-5 1-4 2-3 B. Erythromvcin bite capsule bite capsule
Amounts preferred amount most preferred amount
Erythromycin 25-65 30-50 35-45 polyoxyethylene glycol 5-70 30-60 45-55 glycerin 5-20 7.5-15 10-12.5 flavors 1-10 2-8 3-6
Ciprofloxacin hydrochloride bite capsule
Amounts preferred amount most preferred amount
Ciprofloxacin hydrochloride 25-65 35-55 40-50 glycerin 5-20 7.5-15 10-12.5 polyethylene glycol 20-75 30-65 40-60 flavors 1-10 2-8 3-6
D. zidovudine [fo rmerly called Amounts preferred amount most preferred amount zidovudine 10-50 15-40 25-35 water 30-80 40-75 45-70 ethanol 5-20 7.5-15 9.5-12.5 polyethylene glycol 5-20 7.5-15 9.5-12.5 flavors 0.1-5 1-4 2-3
EXAMPLE 5 Anti-emetics A. Ondansetron hydrochloride lingual spray
Amounts preferred amount most preferred amount ondansetron hydrochloride 1-25 2-20 2.5-15 citric acid monohydrate, 1-10 2-8 2.5-5 sodium citrate dihydrate 0.5-5 1-4 1.25-2.5 water 1-90 5-85 10-75 ethanol 5-30 7.5-20 9.5-15 propylene glycol 5-30 7.5-20 9.5-15 polyethylene glycol 5-30 7.5-20 9.5-15 flavors 1-10 3-8 5-7.5 Dimenhydrinate bite capsule Amounts preferred amount most preferred amount
Dimenhydrinate 0.5-30 2-25 3-15 glycerin 5-20 7.5-15 10-12.5 polyethylene glycol 45-95 50-90 55-85 flavors 1-10 2-8 3-6
C. Dimenhydrinate polar lingual spray
Amounts preferred most preferred amount amount Dimenhydrinat :ee 3-50 4-40 5-35 water 5-90 10-80 15-75 ethanol 1-80 3-50 5-10 polyethylene 1-80 3-50 5-15 glycol Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
EXAMPLE 6
Histamine H-2 receptor antagonists
A. Cimetidine hvdrochloride bite caDsule
Amounts preferred amount most preferred
Cimetidine Hcl 10-60 15-55 25-50 glycerin 5-20 7.5-15 10-12.5 polyethylene glyyccooll 20-90 25-85 30-75 flavors 1-10 2-8 3-6
Famotidine lingual spray Amounts preferred amount most preferred amount Famotidine 1-35 5-30 7-20 water 2.5-25 3-20 5-10
L-aspartic acid 0.1-20 1-15 5-10 polyethylene glycol 20-97 30-95 50-85 flavors 0.1-10 1-7.5 2-5 Famotidine non-polar lingual spray
Amounts preferred most preferred amount amount
Famotidine 1-35 5-30 7-20
Soya oil 10-50 15-40 15-20
Butane 15-80 30-75 45-70 polyoxyethyl- 10-50 15-40 15-20 ated oleic glycerides flavors 0.1-5 1-4 2-3
EXAMPLE 7 Barbiturates
A. Phenytoin sodium lingual spray
Amounts preferred amount most preferred amount
Phenytoin sodium 10-60 15-55 20-40 water 2.5-25 3-20 5-10 ethanol 5-30 7.5-20 9.5-15 propylene glycol 5-30 7.5-20 9.5-15 polyethylene glycol 5-30 7.5-20 9.5-15 flavors 1-10 3-8 5-7.5
B. Phenvtoin non-pol ar lingual spray
Amounts preferred most preferred amount amount
Phenytoin 5-45 10-40 15-35 migylol 10-50 15-40 15-20
Butane 15-80 30-75 60-70 polyoxyethyl- 10-50 15-40 15-20 ated oleic glycerides flavors 0.1-10 1-8 5-7.5 EXAMPLE 8 Prostaglandins
Carboprost thromethamine lingual spray
Amounts preferred amount most preferred amount
Carboprost thromethamine 0.05-5 0.1-3 0.25-2.5 water 50-95 60-80 65-75 ethanol 5-20 7.5-15 9.5-12.5 polyethylene glycol 5-20 7.5-15 9.5-12.5 sodium chloride 1-20 3-15 4-8 flavors 0.1-5 1-4 2-3
Ph is adjusted with sodium hydroxide and/or hydrochloric acid
Carboprost non-polar lingual spray
Amounts preferred most preferred amount amount
Carboprost 0.05-5 0.1-3 0.25-2.5 migylol 25-50 30-45 35-40
Butane 5-60 10-50 20-35 polyoxyethyl- 25-50 30-45 35-40 ated oleic glycerides flavors 0.1-10 1-8 5-7.5
EXAMPLE 9 Neutraceuticals Carnitine as bite capsule (contents are a paste)
Amounts preferred amount most preferred amount
Carnitine fumarate 6-80 30-70 45-65 soya oil 7.5-50 10-40 12.5-35 soya lecithin 0.001-1.0 0.005-0.5 .01-0.1
Soya fats 7.5-50 10-40 12.5-35 flavors 1-10 2-8 3-6 Valerian as lingual spray Amounts preferred amount most preferred amount
Valerian extract 01-10 02-7 025-5 water 50-95 60-80 65-75 ethanol 5-20 75-15 95-125 polyethylene glycol 5-20 75-15 95-125 flavors 1-10 2-8 3-6
B Echinacea as bite capsule Amounts preferred amount most preferred amount
Echinacea extract 30-85 40-75 45-55 soya oil 7550 10-40 125-35 soya lecithin 0001 1 0 0005-05 01-01
Soya fats 75-50 10-40 125-35 flavors 1-10 2-8 3-6
Mixtures of ingredients Amounts preferred amount most preferred amount
Magnesium oxide 15-40 20-35 25-30 Chromium picolinate 001-1 0 002-05 025-075 folic acid 025-30 005-20 025-05 vitamin B-12 001-1 0 002-05 025-075 vitamin E 15-40 20-35 25-30
Soya oil 10-40 125-35 15-20 soya lecithin 01-5 02-4 05-15 soya fat 10-40 15-35 175-20
EXAMPLE 10 Sleep Inducers (also CNS active amine) Djphenhvdramine hydrochloride lingual spray
Amounts preferred most preferred amount amount
Diphenhydramine 3-50 4-40 5-35 Hcl water 5-90 10-80 50-75 ethanol 1-80 3-50 5-10 polyethylene 1-80 3-50 5-15 glycol
Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
EXAMPLE 11 Anti-Asthmatics-Bronchodilators Isoproterenol Hydrochloride as polar lingual spray
Amounts preferred most preferred amount amount
Isoproterenol 0.1-10 0.2-7.5 0.5-6
Hydrochloride water 5-90 10-80 50-75 ethanol 1-80 3-50 5-10 polyethylene 1-80 3-50 5-15 glycol
Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3 B. Terbutaline sulfate as polar lingual spray
Amounts preferred most preferred amount amount
Terbutaline 0.1-10 0.2-7.5 0.5-6 sulfate water 5-90 10-80 50-75 ethanol 1-10 2-8 2.5-5
Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3
C. Terbutaline as non -polar lingual spray
Amounts preferred most preferred amount amount
Terbutaline 0.1-10 0.2-7.5 0.5-6 migylol 25-50 30-45 35-40 isobutane 5-60 10-50 20-35 polyoxyethylated 25-50 30-45 35-40 oleic glycerid< 3S flavors 0.1-10 1-8 5-7.5
D. Theophvlline polar bite capsule
Amounts preferred most preferred amount amount
Theophylline 5-50 10-40 15-30 polyethylene 20-60 25-50 30-40 glycol glycerin 25-50 35-45 30-40 propylene glycol 25-50 35-45 30-40 flavors 0.1-5 1-4 2-3 E. Albuterol sulfate as polar lingual spray
Amounts preferred most preferred amount amount
Albuterol sulfate 0.1-10 0.2-7.5 0.5-6 water 5-90 10-80 50-75 ethanol 1-10 2-8 2.5-5
Sorbitol 0.1-5 0.2-4 0.4-1.0 aspartame 0.01-0.5 0.02-0.4 0.04-0.1 flavors 0.1-5 1-4 2-3

Claims

WHAT IS CLAIMED IS:
1 . A buccal aerosol spray composition for transmucosal administration of a pharmacologically active compound provided that where the said active compound is soluble in a pharmacologically acceptable polar solvent said composition comprises in weight % of total composition: aqueous polar solvent 30-99.69%, active compound 0.001 -60%, and where said active compound is soluble in a pharmacologically acceptable non-polar solvent said composition comprises in weight % of total composition: pharmaceutically acceptable propellant selected from the group consisting of C3.8 hydrocarbon of a linear or branched configuration 50-80%, non-polar solvent 20-85 %, active compound 0.05-50%, wherein the active compound is selected from the group consisting of bio- logically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostoglandins, anti-asthmatics, bronchial dilators and neutraceuticals.
2. The composition of claim 1 additionally comprising, by weight of total composition: flavoring agent 0.1 -10% .
3. The composition of claim 1 comprising: polar solvent 37- 98.58%, active compound 0.0005-55 %, flavoring agent 0.5-8%.
4. The composition of claim 1 comprising: polar solvent 60.9-97.06%, active compound 0.01 -40%, flavoring agent 0.75-7.5 %.
5. The composition of Claim 1 wherein the polar solvent is selected from the group consisting of low molecular weight polyethylene- glycols (PEG) of 400-1000 MW, C2-C8 mono- and poly-alcohols, and alcohols of C7-C18 hydrocarbons of a linear or branched configuration.
6. The composition of Claim 1 wherein the solvent is aqueous ethylene glycol.
7. The composition of Claim 1 wherein the solvent is aqueous ethanol.
8. The composition of Claim 1 wherein the active compound is selected from the group consisting of cyclosporin, clozapine, zidevudine, erythromycin, odansetron, cimetidine, phenytoin, carboprost thromethamine, valerian and isoproterenol in their nonionized form or as the pharmaceutically acceptable salts thereof.
9. The composition of Claim 2 wherein the flavoring agents are selected from the group consisting of synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, sweeteners and combinations thereof.
10. The composition of Claim 2 of the formulation: polar solvent 75-85%, cyclosporin 1 5-25%, flavoring agent 0.1 -5%.
1 1 . The composition of Claim 2 of the formulation: polar solvent 75-84%, odansitron hydrochloride 2.5- 1 5 %, flavoring agent 1 -10%.
12. A method of administering a pharmacologically active compound to a mammal in needed of same, by spraying the oral mucosa of said mammal with a composition of claim 1 .
1 3. The method of claim 1 2 wherein the amount of spray administered is predetermined.
14. The composition of claim 1 comprising: propellant 10-25 %, non-polar solvent 25-89.95%, active compound 0.1 -40%, flavoring agent
1 -8%.
1 5. The composition of claim 1 comprising: propellant 20-70%, non-polar solvent 30-74.75 %, active compound 0.25-35%, flavoring agent 2-7.5%.
1 6. The composition of Claim 1 wherein the propellant is propane, N-butane, iso-butane, N-pentane, iso-pentane, or neo-pentane, and mixtures thereof.
1 7. The composition of Claim 1 wherein the propellant is n-butane or iso-butane and has a water content of no more than 0.2% and oxidizing agents, reducing agents, and Lewis acids or bases content in a concentration of less than 0.1 %.
1 8. The composition of Claim 1 wherein the solvent is a selected from the group consisting of (C2-C24) fatty acid 1C2-C6) esters, C7-C18 hydrocarbons of a linear or branched configuration, and C2-C6 alkanoyl esters, and triglycerides of the corresponding acids.
19. The composition of Claim 1 wherein the solvent is miglyol.
20. The composition of Claim 1 of the formulation: propellant 1 5-80%, non-polar solvent 20-85 %, clozepine 0.5-30%, flavoring agent 1 -5%.
21 . The composition of Claim 1 of the formulation: propellant 1 5-80%, non-polar solvent 20-85%, zidovudine 25-35 %, flavoring agent 0.1 -5%.
22. The composition of Claim 1 of the formulation: propellant 5-
60%, non-polar solvent 1 5-98.5%, carboprost 0.05-5%, flavoring agent 0.1 -10%.
23. The composition of Claim 1 of the formulation: propellant 5-60%, non-polar solvent 20-94.8%, terbutaline 0.5-6%, flavoring agent
0.01 -10%.
24. A soft bite gelatin capsule for transmucosal administration of a pharmacologically active compound, where said active compound is at least partially soluble in a pharmacologically acceptable polar solvent, having charged thereto a fill composition comprising in weight % of total fill composition: polar solvent 25-99.89%, emulsifier 0-20%, active compound 0.01 -65%, and where said active compound is at least partially soluble in a pharmaco- logically acceptable non-polar solvent, having charged thereto a fill composition comprising in weight % of total fill composition: non-polar solvent 4-99.99%, emulsifier 0-20%, active compound 0.01 -80%, wherein the active compound is selected from the group consisting of biologically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostoglandins and neutraceuticals, provided that said composition contains less than 10% of water.
25. The composition of Claim 24 wherein the active compound is selected from the group consisting of cyclosporin, clozapine, glyburide, erythromycin, odansetron, cimetidine, phenytoin, carboprostthromethamine and valerian in their nonionized form or as the pharmaceutically acceptable salts thereof.
26. The capsule of Claim 24 wherein the active compound is in their nonionized form or as the free base of the pharmaceutically acceptable salts thereof.
27. The capsule of Claim 24 wherein the flavoring agents are synthetic or natural oil of peppermint, oil of spearmint, citrus oil, fruit flavors, or sweeteners and combinations thereof.
28. The capsule of claim 24 additionally comprising, by weight of the fill composition: flavoring agent 0.1 -10%.
29. The soft bite gelatin capsule of Claim 24 comprising as the fill composition: polar solvent 37-98.95 %, emulsifier 0- 1 5 %, active compound 0.025-55%, flavoring agent 1 -8%.
30. The soft bite gelatin capsule of Claim 24 comprising as the fill composition: polar solvent 44-96.925%, emulsifier 0-10%, active compound 0.075-50%, flavoring agent 2-6%.
31 . The capsule of Claim 24 wherein the solvent is selected from the group consisting of low molecular weight polyethyleneglycols (PEG) of 400-1000 MW, C2-C8 mono- and poly-alcohols, and alcohols of C7-C18 hydrocarbons of a linear or branched configuration.
32. The capsule of Claim 24 wherein the solvent is selected from low molecular weight polyethyleneglycols (PEG) of 400-600 MW.
33. The capsule of Claim 24 comprising: non-polar solvent 21 .5- 99.975%, emulsifier 0-1 5%, active compound 0.025-70%, flavoring agent
1 -8%.
34. The capsule of Claim 24 comprising: non-polar solvent 28.5-97.9%, emulsifier 0-10%, active compound 0.1 -65%, flavoring agent 2-6%.
35. The capsule of Claim 24 wherein the solvent is selected from the group consisting of (C2-C24) fatty acid (C2-C6) esters, C7-C18 hydrocarbons of a linear or branched configuration, and C2-C6 alkanoyl esters, and triglycerides of the corresponding acids.
36. The capsule of Claim 24 comprising as the fill composition the formulation: polar solvent 75-99%, emulsifier 0-20%, cyclosporine 1 5-25%, flavoring agent 0.1 -6%.
37. The capsule of Claim 24 comprising as the fill composition the formulation: polar solvent 25-99.89%, emulsifier 0-20%, sumatriptan succinate 0.01 -5 %, flavoring agent 0.1 -10%.
38. The capsule of Claim 24 comprising as the fill composition the formulation: polar solvent 30-89%, emulsifier 0-20%, cimetidine hydrochloride 10-60%, flavoring agent 1 -10%.
39. The capsule of Claim 24 comprising as the fill composition the formulation: polar solvent 60-98.5 %, emuisifier 0-20%, dimenhydrinate 0.5- 30%, flavoring agent 1 -10%.
40. The capsule of Claim 24 comprising as the fill composition the formulation: polar solvent 45-94.9%, emulsifier 0-20%, theophylline 5.0- 50%, flavoring agent 0.5-5%.
41 . The capsule of Claim 24 comprising as the fill composition the formulation: polar solvent 7.5-99.8%, emulsifier 0-20%, carnitine fumarate 6-80%, flavoring agent 1 -10%.
42. A buccal pump spray composition for transmucosal administra- tion of a pharmacologically active compound where said active compound is soluble in a pharmacologically acceptable non-polar solvent said composition comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, flavoring agent 0.1 -10%, wherein the active compound is selected from the group consisting of bio- logically active peptides, central nervous system active amines, sulfonyl ureas, antibiotics, antifungals, antivirals, sleep inducers, antiasthmatics, bronchial dilators, antiemetics, histamine H-2 receptor antagonists, barbiturates, prostoglandins and neutraceuticals.
43. A buccal pump spray composition fortransmucosal administration of a pharmacologically active compound where said active compound is soluble in a pharmacologically acceptable non-polar solvent said composition comprises in weight % of total composition: non-polar solvent 30-99.69%, active compound 0.005-55%, flavoring agent 0.1 -10%, wherein the active compound is selected from the group consisting of antihistamines, alkaloids, hormones, benzodiazepines and narcotic analgesics.
PCT/US1997/017899 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule WO1999016417A1 (en)

Priority Applications (72)

Application Number Priority Date Filing Date Title
EP07023005A EP1952802A3 (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule
PCT/US1997/017899 WO1999016417A1 (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule
EP00109347A EP1029536B1 (en) 1997-10-01 1997-10-01 Buccal non-polar spray
EP97911621A EP1019019A1 (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule
ES00109347T ES2293875T3 (en) 1997-10-01 1997-10-01 NON-POLAR ORAL SPRAY.
DE69738333T DE69738333T2 (en) 1997-10-01 1997-10-01 Non-polar spray for buccal administration
CA2306024A CA2306024C (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule
JP2000513555A JP2001517689A (en) 1997-10-01 1997-10-01 Polar or non-polar buccal spray or capsule
EP00109357A EP1036561A1 (en) 1997-10-01 1997-10-01 Buccal, non-polar spray
AU48946/97A AU4894697A (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule
EP20080020267 EP2042161A1 (en) 1997-10-01 1997-10-01 Propellant-free spray composition comprising anti-emetic agent
US10/100,156 US6676931B2 (en) 1997-10-01 2002-03-18 Buccal, polar and non-polar spray or capsule
US10/230,085 US20030095926A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US10/230,060 US20030077227A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US10/230,080 US20030082107A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US10/230,072 US20030190286A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US10/230,073 US20030077228A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US10/230,084 US20030095925A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US10/230,059 US20030185761A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US10/230,086 US20030095927A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US10/230,075 US20030077229A1 (en) 1997-10-01 2002-08-29 Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US10/327,195 US6998110B2 (en) 1997-10-01 2002-12-24 Buccal, polar and non-polar spray or capsule
US10/663,817 US20040062716A1 (en) 1997-10-01 2003-09-17 Buccal, polar and non-polar spray of capsule
US10/671,710 US20040136913A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing sumatriptan
US10/671,719 US20040136915A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing atropine
US10/671,720 US20040141923A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing alprazolam
US10/671,709 US20050163719A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing diazepam
US10/671,708 US20050180923A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing testosterone
US10/671,717 US20040136914A1 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing ondansetron
US10/671,715 US7632517B2 (en) 1997-10-01 2003-09-29 Buccal, polar and non-polar spray containing zolpidem
US10/726,625 US6969508B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US10/726,585 US6977070B2 (en) 1997-10-01 2003-12-04 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US10/834,815 US20050002867A1 (en) 1997-10-01 2004-04-27 Buccal, polar and non-polar sprays containing propofol
US10/928,989 US20050025714A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US10/928,952 US20050025712A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US10/928,997 US20050025717A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US10/928,995 US20050025715A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US10/928,979 US20050025713A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US10/929,001 US20050142069A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US10/928,996 US20050025716A1 (en) 1997-10-01 2004-08-27 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US11/211,488 US20050281752A1 (en) 1997-10-01 2005-08-26 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US11/211,487 US20050287075A1 (en) 1997-10-01 2005-08-26 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US11/211,549 US20050281753A1 (en) 1997-10-01 2005-08-26 Buccal, polar and non-polar spray or capsule
US11/366,663 US20060165604A1 (en) 1997-10-01 2006-03-03 Buccal, polar and non-polar spray containing sumatriptan
US11/384,444 US20060159624A1 (en) 1997-10-01 2006-03-21 Buccal, polar and non-polar spray containing zolpidem
US11/391,297 US20060171896A1 (en) 1997-10-01 2006-03-29 Buccal, polar and non-polar spray containing alprazolam
US11/429,953 US20060198790A1 (en) 1997-10-01 2006-05-09 Buccal, polar and non-polar spray containing ondansetron
US11/440,095 US20060210484A1 (en) 1997-10-01 2006-05-25 Buccal, polar and non-polar spray containing testosterone
US11/442,137 US20060222597A1 (en) 1997-10-01 2006-05-30 Buccal, polar and non-polar sprays containing propofol
US11/443,253 US20060216240A1 (en) 1997-10-01 2006-05-31 Buccal, polar and non-polar spray containing zolpidem
US11/443,254 US20060216241A1 (en) 1997-10-01 2006-05-31 Buccal, polar and non-polar spray containing diazepam
US11/443,260 US20070048229A1 (en) 1997-10-01 2006-05-31 Buccal, polar and non-polar spray containing atropine
US11/929,368 US20080170995A1 (en) 1997-10-01 2007-10-30 Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US12/350,602 US20090162297A1 (en) 1997-10-01 2009-01-08 Buccal, polar and non-polar spray containing ondansetron
US12/350,898 US20090118170A1 (en) 1997-10-01 2009-01-08 Buccal, polar and non-polar spray or capsule
US12/350,915 US20090131514A1 (en) 1997-10-01 2009-01-08 Buccal, polar and non-polar sprays containing propofol
US12/351,275 US20090186099A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US12/351,179 US20090186035A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US12/351,606 US20090124554A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US12/351,576 US20090162298A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray containing sumatriptan
US12/351,490 US20090123387A1 (en) 1997-10-01 2009-01-09 Buccal, polar and non-polar spray or capsule containing cardiovascular or reneal drugs
US12/394,903 US20090162300A1 (en) 1997-10-01 2009-02-27 Buccal, polar and non-polar spray containing alprazolam
US12/576,457 US8236285B2 (en) 1997-10-01 2009-10-09 Buccal, polar and non-polar spray containing zolpidem
US12/632,719 US20100152262A1 (en) 1997-10-01 2009-12-07 Buccal, polar and non-polar spray containing ondansetron
US12/692,213 US20100209541A1 (en) 1997-10-01 2010-01-22 Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US13/197,207 US20120027879A1 (en) 1997-10-01 2011-08-03 Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US13/208,429 US20110293536A1 (en) 1997-10-01 2011-08-12 Buccal, polar and non-polar spray containing zolipidem
US13/445,331 US9078816B2 (en) 1997-10-01 2012-04-12 Buccal, polar and non-polar spray containing ondansetron
US13/450,987 US20120202866A1 (en) 1997-10-01 2012-04-19 Buccal, polar and non-polar spray containing ondansetron
US13/467,441 US20120252846A1 (en) 1997-10-01 2012-05-09 Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US13/683,530 US20130199519A1 (en) 1997-10-01 2012-11-21 Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US14/218,518 US20140200516A1 (en) 1997-10-01 2014-03-18 Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1997/017899 WO1999016417A1 (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US53711800A Continuation-In-Part 1997-10-01 2000-03-29

Publications (1)

Publication Number Publication Date
WO1999016417A1 true WO1999016417A1 (en) 1999-04-08

Family

ID=22261809

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/017899 WO1999016417A1 (en) 1997-10-01 1997-10-01 Buccal, polar and non-polar spray or capsule

Country Status (8)

Country Link
US (5) US6676931B2 (en)
EP (5) EP1029536B1 (en)
JP (1) JP2001517689A (en)
AU (1) AU4894697A (en)
CA (1) CA2306024C (en)
DE (1) DE69738333T2 (en)
ES (1) ES2293875T3 (en)
WO (1) WO1999016417A1 (en)

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6255294B1 (en) * 1998-12-28 2001-07-03 Allergy Limited Cyanocobalamin (vitamin B12) treatment in allergic disease
US6432383B1 (en) 2000-03-30 2002-08-13 Generex Pharmaceuticals Incorporated Method for administering insulin
US6451286B1 (en) 1998-12-21 2002-09-17 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary administration comprising an alkali metal alkyl sulfate and at least three micelle-forming compounds
EP1307243A2 (en) * 2000-05-01 2003-05-07 Aeropharm Technology Incorporated A medicinal aerosol formulation
WO2004019912A2 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar or non-polar spray or capsule containing drugs for treating an infectious disease or cancer
WO2004019910A2 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
WO2004019911A2 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar or non-polar spray or capsule containing drugs for treating endocrine disorders
WO2004019903A1 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs fortreating metabolic disorders
WO2004019904A1 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
WO2004035021A2 (en) * 2002-08-29 2004-04-29 Novadel Pharma Inc. Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
WO2004043428A2 (en) * 2002-08-29 2004-05-27 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
WO2004019909A3 (en) * 2002-08-29 2004-07-08 Novadel Pharma Inc Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
EP1444976A1 (en) * 2003-02-10 2004-08-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule
US6846495B2 (en) 1999-01-11 2005-01-25 The Procter & Gamble Company Compositions having improved delivery of actives
WO2004080382A3 (en) * 2003-03-11 2005-03-24 Sirus Pharmaceuticals Ltd Novel compositions containing fentanyl
WO2005037949A2 (en) * 2003-10-07 2005-04-28 Chrysalis Technologies Incorporated Aerosol formulations of butalbital, lorazepam, ipratropium, baclofen, morphine and scopolamine
WO2005049061A2 (en) * 2003-11-20 2005-06-02 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
WO2005123043A2 (en) * 2004-06-10 2005-12-29 Duramed Pharmaceuticals, Inc. Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same
US6998110B2 (en) 1997-10-01 2006-02-14 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule
US7070799B1 (en) 1998-02-10 2006-07-04 Generex Pharmaceuticals, Inc. Method for administering insulin to the buccal region
US7138133B2 (en) 2001-10-10 2006-11-21 The Procter & Gamble Company Orally administered liquid compositions
US7253155B2 (en) 2001-10-05 2007-08-07 Combinatorx, Inc. Combinations for the treatment of immunoinflammatory disorders
WO2007124869A2 (en) * 2006-05-02 2007-11-08 Bayer Animal Health Gmbh Liquid pharmaceutical formulation
US7348403B2 (en) 2002-12-09 2008-03-25 The Trustees Of Columbia University In The City Of New York Peptides and methods for deactivation of organophosphorus-based nerve agents and insecticides
US7658945B2 (en) 2004-02-17 2010-02-09 Transcept Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
WO2011064316A2 (en) 2009-11-25 2011-06-03 Paolo Botti Mucosal delivery of peptides
US8080553B2 (en) 2003-10-15 2011-12-20 Zalicus Inc. Methods and reagents for the treatment of immunoinflammatory disorders
US8114959B2 (en) 2003-06-03 2012-02-14 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8269040B2 (en) 1999-04-06 2012-09-18 Wyeth Llc Derivatives of venlafaxine and methods of preparing and using the same
EP2526971A1 (en) 2011-05-25 2012-11-28 ArisGen SA Mucosal delivery of drugs
US8614181B2 (en) 2003-06-03 2013-12-24 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8642662B2 (en) 1998-12-01 2014-02-04 Sunovion Pharmaceuticals Inc. Methods of using derivatives of (−)-venlafaxine
US8710181B2 (en) 2004-08-31 2014-04-29 Novo Nordisk A/S Use of tris(hydroxymethyl) aminomethane for the stabilization of peptides, polypeptides and proteins
US8748376B2 (en) 2004-11-12 2014-06-10 Novo Nordisk A/S Stable formulations of peptides
US8846618B2 (en) 2001-06-28 2014-09-30 Novo Nordisk A/S Stable formulation of modified GLP-1
US9078816B2 (en) 1997-10-01 2015-07-14 Suda Ltd. Buccal, polar and non-polar spray containing ondansetron
EP1360169B2 (en) † 2001-02-12 2017-05-24 Wyeth LLC Succinate salt of o-desmethyl-venlafaxine
US10004684B2 (en) 2001-02-14 2018-06-26 Gw Pharma Limited Pharmaceutical formulations
WO2020075183A1 (en) 2018-10-08 2020-04-16 Troikaa Pharmaceuticals Limited Oromucosal solutions of zolpidem or pharmaceutically acceptable salts thereof
CN113009057A (en) * 2020-10-22 2021-06-22 重庆医科大学 Method for detecting neonicotinoid insecticides and metabolites in urine by solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry
US11318191B2 (en) 2020-02-18 2022-05-03 Novo Nordisk A/S GLP-1 compositions and uses thereof
US11752198B2 (en) 2017-08-24 2023-09-12 Novo Nordisk A/S GLP-1 compositions and uses thereof

Families Citing this family (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6428771B1 (en) * 1995-05-15 2002-08-06 Pharmaceutical Discovery Corporation Method for drug delivery to the pulmonary system
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US7632517B2 (en) 1997-10-01 2009-12-15 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20090162300A1 (en) * 1997-10-01 2009-06-25 Dugger Iii Harry A Buccal, polar and non-polar spray containing alprazolam
US20040136913A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing sumatriptan
US20050281752A1 (en) * 1997-10-01 2005-12-22 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20040141923A1 (en) * 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US20050287075A1 (en) * 1997-10-01 2005-12-29 Dugger Harry A Iii Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US9006175B2 (en) 1999-06-29 2015-04-14 Mannkind Corporation Potentiation of glucose elimination
EP2280004B1 (en) * 1999-06-29 2016-04-20 MannKind Corporation Pharmaceutical formulations comprising insulin complexed with a diketopiperazine
US20030072717A1 (en) * 2001-02-23 2003-04-17 Vapotronics, Inc. Inhalation device having an optimized air flow path
CN1236831C (en) * 2001-05-21 2006-01-18 茵捷特数码浮质有限公司 Compositions for protein delivery via the pulmonary route
WO2003080149A2 (en) 2002-03-20 2003-10-02 Mannkind Corporation Inhalation apparatus
US20060062812A1 (en) * 2003-03-11 2006-03-23 Calvin Ross Novel compositions
US7683029B2 (en) * 2003-05-07 2010-03-23 Philip Morris Usa Inc. Liquid aerosol formulations containing insulin and aerosol generating devices and methods for generating aerosolized insulin
NZ527142A (en) * 2003-07-23 2006-03-31 Douglas Pharmaceuticals Ltd A stable suspension formulation
US7338171B2 (en) * 2003-10-27 2008-03-04 Jen-Chuen Hsieh Method and apparatus for visual drive control
AU2005204378B2 (en) * 2004-01-12 2009-01-22 Mannkind Corporation A method of reducing serum proinsulin levels in type 2 diabetics
US7658721B2 (en) * 2004-01-16 2010-02-09 Biodel Inc. Sublingual drug delivery device
ES2398838T3 (en) * 2004-03-12 2013-03-22 Biodel, Inc. Fast-acting drug delivery compositions
US20080085298A1 (en) * 2004-03-12 2008-04-10 Biodel, Inc. Rapid Mucosal Gel or Film Insulin Compositions
US20080248999A1 (en) * 2007-04-04 2008-10-09 Biodel Inc. Amylin formulations
US20080096800A1 (en) * 2004-03-12 2008-04-24 Biodel, Inc. Rapid mucosal gel or film insulin compositions
US20080090753A1 (en) 2004-03-12 2008-04-17 Biodel, Inc. Rapid Acting Injectable Insulin Compositions
CN101132694B (en) * 2004-04-30 2011-10-05 祥丰医疗有限公司 Medical device with coating for capturing genetically-altered cells and methods of using same
JP5078014B2 (en) 2004-08-20 2012-11-21 マンカインド コーポレイション Catalytic reaction of diketopiperazine synthesis.
MX2007002189A (en) 2004-08-23 2008-01-11 Mannkind Corp Diketopiperazine salts, diketomorpholine salts or diketodioxane salts for drug delivery.
JP5577021B2 (en) 2005-02-17 2014-08-20 アボット・ラボラトリーズ Transmucosal administration of pharmaceutical compositions for treating and preventing disorders in animals
US20070287740A1 (en) * 2005-05-25 2007-12-13 Transcept Pharmaceuticals, Inc. Compositions and methods of treating middle-of-the night insomnia
US20070225322A1 (en) * 2005-05-25 2007-09-27 Transoral Pharmaceuticals, Inc. Compositions and methods for treating middle-of-the night insomnia
CA2609330A1 (en) * 2005-05-25 2006-11-30 Transcept Pharmaceuticals, Inc. Solid compositions and methods for treating middle-of-the night insomnia
US7803404B2 (en) 2005-09-14 2010-09-28 Mannkind Corporation Method of drug formulation based on increasing the affinity of active agents for crystalline microparticle surfaces
US8084420B2 (en) * 2005-09-29 2011-12-27 Biodel Inc. Rapid acting and long acting insulin combination formulations
US7713929B2 (en) 2006-04-12 2010-05-11 Biodel Inc. Rapid acting and long acting insulin combination formulations
US20070086952A1 (en) * 2005-09-29 2007-04-19 Biodel, Inc. Rapid Acting and Prolonged Acting Inhalable Insulin Preparations
RU2432950C2 (en) 2006-01-25 2011-11-10 Инсис Терапьютикс Инк. Sublingual fentanyl-based spray
IN2015DN00888A (en) 2006-02-22 2015-07-10 Mannkind Corp
MX2008013165A (en) * 2006-04-12 2009-01-29 Biodel Inc Rapid acting and long acting insulin combination formulations.
EP2015632B1 (en) * 2006-04-19 2015-12-02 Mist Pharmaceuticals, LLC Stable hydroalcoholic oral spray formulations and methods
DE102006032426A1 (en) * 2006-07-13 2008-01-17 Neuraxpharm Arzneimittel Gmbh U. Co. Kg Use of a composition comprising e.g. clozapine and quetiapine; benzyl- and/or phenylethyl alcohol; propylene glycol; ethereal oil; and polyethylene glycol, for preparing an orally administering solution to treat schizophrenia
DE102006032427A1 (en) * 2006-07-13 2008-01-17 Neuraxpharm Arzneimittel Gmbh U. Co. Kg Use of composition comprising e.g. clozapine, quetiapine, olanzapine, benzyl- and/or phenylethyl alcohol, ethanol, ethereal oil, sweetener, and polyethylene glycol, for preparing an orally administering solution to treat schizophrenia
JP2009544715A (en) * 2006-07-28 2009-12-17 ノヴァデル ファーマ インコーポレイテッド Oral spray formulation and method for anti-migraine
EP2124556B1 (en) 2006-10-09 2014-09-03 Charleston Laboratories, Inc. Pharmaceutical compositions
US20080171089A1 (en) * 2006-12-22 2008-07-17 Blondino Frank E Stable anti-nausea oral spray formulations and methods
WO2008091588A1 (en) 2007-01-22 2008-07-31 Targacept, Inc. Intranasal, buccal, and sublingual administration of metanicotine analogs
EP2152247A4 (en) * 2007-05-10 2012-12-26 Novadel Pharma Inc Anti-insomnia compositions and methods
PL2180844T3 (en) 2007-08-02 2018-07-31 Insys Development Company, Inc. Sublingual fentanyl spray
US7985325B2 (en) * 2007-10-30 2011-07-26 Novellus Systems, Inc. Closed contact electroplating cup assembly
FR2925333B1 (en) * 2007-12-19 2012-04-13 Farid Bennis PHARMACEUTICAL COMPOSITIONS COMPRISING AT LEAST ONE PROTEIN ACTIVE INGREDIENT PROTECTS DIGESTIVE ENZYMES
WO2009089181A1 (en) * 2008-01-04 2009-07-16 Blodel, Inc. Insulin formulations for insulin release as a function of tissue glucose levels
CA3066426A1 (en) 2008-01-09 2009-07-16 Charleston Laboratories, Inc. Pharmaceutical compositions comprising an antiemetic and an opioid analgesic
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
KR101933816B1 (en) 2008-06-13 2019-03-29 맨카인드 코포레이션 A dry powder inhaler and system for drug delivery
WO2009155581A1 (en) 2008-06-20 2009-12-23 Mannkind Corporation An interactive apparatus and method for real-time profiling of inhalation efforts
TWI494123B (en) 2008-08-11 2015-08-01 Mannkind Corp Use of ultrarapid acting insulin
US8314106B2 (en) 2008-12-29 2012-11-20 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
US9060927B2 (en) * 2009-03-03 2015-06-23 Biodel Inc. Insulin formulations for rapid uptake
PL2405963T3 (en) 2009-03-11 2014-04-30 Mannkind Corp Apparatus, system and method for measuring resistance of an inhaler
BRPI1013154B1 (en) 2009-06-12 2020-04-07 Mannkind Corp MICROPARTICLES OF DICETOPIPERAZINE WITH SPECIFIC SURFACE AREAS DEFINED, DRY POWDER UNDERSTANDING THE REFERRED MICROPARTICLES, METHOD FOR FORMATION OF THE REFERENCESMICROPARTICLES AND THE FORMATION OF MICROPARTYSTEMS
CA2767576C (en) 2009-07-08 2020-03-10 Charleston Laboratories Inc. Pharmaceutical compositions comprising an antiemetic and an opioid analgesic
CA2778698A1 (en) 2009-11-03 2011-05-12 Mannkind Corporation An apparatus and method for simulating inhalation efforts
JP5535679B2 (en) * 2010-02-18 2014-07-02 株式会社トクヤマ Method for producing trichlorosilane
WO2011121496A1 (en) 2010-03-31 2011-10-06 Wockhardt Limited Composition comprising insulin and herbal oil for transdermal or transmucosal administration
MX359281B (en) 2010-06-21 2018-09-21 Mannkind Corp Dry powder drug delivery system and methods.
MX353285B (en) 2011-04-01 2018-01-05 Mannkind Corp Blister package for pharmaceutical cartridges.
WO2012174472A1 (en) 2011-06-17 2012-12-20 Mannkind Corporation High capacity diketopiperazine microparticles
IN2014DN03093A (en) 2011-10-24 2015-05-15 Mannkind Corp
SG10201605800UA (en) 2012-07-12 2016-09-29 Mannkind Corp Dry powder drug delivery system and methods
WO2014066856A1 (en) 2012-10-26 2014-05-01 Mannkind Corporation Inhalable influenza vaccine compositions and methods
KR102499439B1 (en) 2013-03-15 2023-02-13 맨카인드 코포레이션 Microcrystalline diketopiperazine compositions and methods
CA2918369C (en) 2013-07-18 2021-06-29 Mannkind Corporation Heat-stable dry powder pharmaceutical compositions and methods
WO2015021064A1 (en) 2013-08-05 2015-02-12 Mannkind Corporation Insufflation apparatus and methods
EP3068376A4 (en) * 2013-11-14 2017-06-07 Insys Pharma, Inc. Ondansetron sublingual spray formulation
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
US10172833B2 (en) 2015-08-11 2019-01-08 Insys Development Company, Inc. Sublingual ondansetron spray
JP2019507181A (en) 2016-03-04 2019-03-14 チャールストン ラボラトリーズ，インコーポレイテッド Pharmaceutical composition

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3338978A1 (en) * 1982-10-29 1984-05-03 Basf Ag, 6700 Ludwigshafen Verapamil and gallopamil and their physiologically tolerated salts for application onto the mucous membranes of the mouth, of the naso-pharyngeal space and of the rectum for absorption
DE3246081A1 (en) * 1982-12-13 1984-06-14 G. Pohl-Boskamp GmbH & Co Chemisch-pharmazeutische Fabrik, 2214 Hohenlockstedt Nitroglycerin spray
FR2633933A1 (en) * 1988-07-08 1990-01-12 Egyt Gyogyszervegyeszeti Gyar COMPOSITION FOR AEROSOLS CONTAINING NITROGLYCERIN AS ACTIVE INGREDIENT
WO1990001046A1 (en) * 1988-05-02 1990-02-08 Zila Pharmaceuticals, Inc. Compositions and in situ methods for forming films on body tissue
US4935243A (en) * 1988-12-19 1990-06-19 Pharmacaps, Inc. Chewable, edible soft gelatin capsule
DE4007705C1 (en) * 1990-03-10 1991-09-26 G. Pohl-Boskamp Gmbh & Co. Chemisch-Pharmazeutische Fabrik, 2214 Hohenlockstedt, De
EP0471161A1 (en) * 1990-08-17 1992-02-19 Schwarz Pharma Ag Spray container containing nitroglycerin in a hydrophilic aqueous composition
DE4038203A1 (en) * 1990-11-30 1992-06-04 Kali Chemie Pharma Gmbh Pharmaceutical spray-prepn. for admin. of nitrate(s) - esp. for treatment of cardiovascular, disorders, asthma, migraine and colic
EP0656206A1 (en) * 1991-06-10 1995-06-07 Schering Corporation Non-chlorofluorocarbon aerosol formulations
WO1995024893A1 (en) * 1994-03-16 1995-09-21 R.P. Scherer Limited Delivery systems for hydrophobic drugs
WO1997038687A1 (en) * 1996-04-12 1997-10-23 Flemington Pharmaceutical Corporation Buccal, non-polar spray for nitroglycerin
WO1997038663A2 (en) * 1996-04-12 1997-10-23 Flemington Pharmaceutical Corporation Buccal, non-polar spray or capsule

Family Cites Families (97)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE632504A (en) 1962-05-24
US3304230A (en) 1963-02-18 1967-02-14 Revlon Liquid aerosol propellant solutions of fatty acid salts of physiologically active amines
GB1154317A (en) * 1965-06-15 1969-06-04 Higham Stanley Russell Oral Vehicle for Administering Drugs by Buccal Absorption
SU432703A3 (en) 1971-08-24 1974-06-15 Фридрих Боссерт, Вульф Фатер, Курт Бауер
SE7812207L (en) 1977-12-01 1979-06-02 Welsh Nat School Med APPARATUS, PROCEDURE AND MANUFACTURED PRODUCTS FOR USE IN THE ADMINISTRATION OF ANTIHISTAMINES
ZA815698B (en) 1980-08-28 1983-04-27 Lilly Co Eli Intranasal formulation
US4495168A (en) * 1983-08-22 1985-01-22 Basf Wyandotte Corporation Aerosol gel
IT1169873B (en) 1983-10-21 1987-06-03 Prodotti Formenti Srl PHARMACEUTICAL COMPOSITION WITH SYSTEMIC ANTI-COLINESTERASIC, AGONISTIC-COLINERGIC AND ANTI-MUSCARINIC ACTIVITY
GB8501015D0 (en) * 1985-01-16 1985-02-20 Riker Laboratories Inc Drug
DE3522550A1 (en) * 1985-06-24 1987-01-02 Klinge Co Chem Pharm Fab SPRAYABLE PHARMACEUTICAL PREPARATION FOR TOPICAL APPLICATION
EP0213108A3 (en) * 1985-06-26 1987-07-15 Kurt Dr. Burghart Pharmaceutical preparation containing an antihypotonic as the active agent
GB8522453D0 (en) 1985-09-11 1985-10-16 Lilly Industries Ltd Chewable capsules
DE3544692A1 (en) 1985-12-18 1987-06-19 Bayer Ag DIHYDROPYRIDINE SPRAY, METHOD FOR THE PRODUCTION THEREOF AND ITS PHARMACEUTICAL USE
US4689233A (en) 1986-01-06 1987-08-25 Siegfried Aktiengesellschaft Coronary therapeutic agent in the form of soft gelatin capsules
ATE60226T1 (en) * 1986-03-10 1991-02-15 Kurt Burghart PHARMACEUTICAL AND PROCESS FOR PRODUCTION.
US4863970A (en) * 1986-11-14 1989-09-05 Theratech, Inc. Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
JPH0645538B2 (en) 1987-09-30 1994-06-15 日本化薬株式会社 Nitroglycerin spray
DE3738236A1 (en) 1987-11-11 1989-05-24 Euro Celtique Sa BIT CAPSULE
US5719197A (en) * 1988-03-04 1998-02-17 Noven Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5128132A (en) 1988-11-22 1992-07-07 Parnell Pharmaceuticals, Inc. Eriodictyon compositions and methods for treating internal mucous membranes
US5225183A (en) * 1988-12-06 1993-07-06 Riker Laboratories, Inc. Medicinal aerosol formulations
US5776434A (en) 1988-12-06 1998-07-07 Riker Laboratories, Inc. Medicinal aerosol formulations
US5011678A (en) 1989-02-01 1991-04-30 California Biotechnology Inc. Composition and method for administration of pharmaceutically active substances
DE3907414A1 (en) 1989-03-08 1990-09-13 Hoechst Ag THE APPLICATION OF INHALED LOOP DIURETICS FOR THE TREATMENT OF ALLERGEN-INDUCED NASAL REACTIONS
IL94466A (en) * 1989-05-25 1995-01-24 Erba Carlo Spa Pharmaceutical compositions containing n-phenylalkyl substituted alpha-amino carboxamide derivatives, some such novel compounds and their preparation
DE4000770A1 (en) 1990-01-12 1991-07-18 Reynolds Aluminium Deutschland CONNECTION OF THE JOINT BETWEEN BAR AND POST ON A CARRIER FOR ONE OR ON A FAÇADE WALL
ES2094809T3 (en) 1990-03-30 1997-02-01 Yasunori Morimoto ABSORBABLE COMPOSITION BY VIA PERCUTANEA OF MORPHINE CHLORHYDRATE.
DE69129110T2 (en) 1990-05-10 1998-12-10 Bechgaard Int Res PHARMACEUTICAL PREPARATION CONTAINING N-GLYCOFUROLE AND N-ETHYLENE GLYCOL
US5370862A (en) 1990-06-13 1994-12-06 Schwarz Pharma Ag Pharmaceutical hydrophilic spray containing nitroglycerin for treating angina
US5143731A (en) * 1990-08-07 1992-09-01 Mediventures Incorporated Body cavity drug delivery with thermo-irreversible polyoxyalkylene and ionic polysaccharide gels
US5166145A (en) * 1990-09-10 1992-11-24 Alza Corporation Antiemetic therapy
US5135753A (en) 1991-03-12 1992-08-04 Pharmetrix Corporation Method and therapeutic system for smoking cessation
EP0504112A3 (en) * 1991-03-14 1993-04-21 Ciba-Geigy Ag Pharmaceutical aerosol formulations
DE4112303A1 (en) * 1991-04-15 1992-10-22 Minnesota Mining & Mfg Nitroglycerin, propellant gas-free spray prepn. - stored in container in which the steel parts are made of V4A series steels to inhibit nitroglycerin decomposition
CA2109528A1 (en) * 1991-05-01 1992-11-02 Gregory A. Prince A method for treating infectious respiratory diseases
CA2103163C (en) 1991-08-26 1998-10-20 Mou-Ying Fu Lu Compositions and methods for the sublingual or buccal administration of therapeutic agents
GB9118830D0 (en) * 1991-09-03 1991-10-16 Minnesota Mining & Mfg Medical aerosol formulations
DE4132176C2 (en) 1991-09-27 1997-03-13 Ig Spruehtechnik Gmbh Metered aerosols with isobutane as propellant
US5457100A (en) 1991-12-02 1995-10-10 Daniel; David G. Method for treatment of recurrent paroxysmal neuropsychiatric
US5824307A (en) * 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
DK0557129T3 (en) 1992-02-20 1997-04-14 Wielligh Johannes Louw Kot Von Product to help smokers quit smoking
US5294433A (en) * 1992-04-15 1994-03-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis
JP3717925B2 (en) * 1992-09-29 2005-11-16 ネクター セラピューティクス Pulmonary introduction of active fragments of parathyroid hormone
AU5551394A (en) 1992-11-09 1994-06-08 Pharmetrix Corporation Combined analgesic delivery methods for pain management
WO1994013280A1 (en) 1992-12-04 1994-06-23 Mayor Pharmaceutical Laboratories, Inc. Sprayable analgesic composition and method of use
US5981591A (en) 1992-12-04 1999-11-09 Mayor Pharmaceutical Laboratories, Inc. Sprayable analgesic composition and method of use
EP0689424B1 (en) * 1993-03-17 1998-10-14 Minnesota Mining And Manufacturing Company Aerosol formulation containing an ester-, amide-, or mercaptoester-derived dispersing aid
US5362496A (en) 1993-08-04 1994-11-08 Pharmetrix Corporation Method and therapeutic system for smoking cessation
GB9401891D0 (en) * 1994-02-01 1994-03-30 Boots Co Plc Therapeutic agents
US5502076A (en) 1994-03-08 1996-03-26 Hoffmann-La Roche Inc. Dispersing agents for use with hydrofluoroalkane propellants
HU214582B (en) * 1994-07-26 1998-04-28 EGIS Gyógyszergyár Rt. Spayable antihypertensive composition and process for it`s production
US5519059A (en) * 1994-08-17 1996-05-21 Sawaya; Assad S. Antifungal formulation
US5456677A (en) 1994-08-22 1995-10-10 Spector; John E. Method for oral spray administration of caffeine
GB9423511D0 (en) * 1994-11-22 1995-01-11 Glaxo Wellcome Inc Compositions
NZ280610A (en) 1994-12-29 1997-08-22 Mcneil Ppc Inc Soft gelatin-like pharmaceutical carrier: gelled polyethylene glycol and dispersed active agent
US5563177A (en) * 1995-01-30 1996-10-08 American Home Products Corporation Taste masking guaifenesin containing liquids
US5908611A (en) * 1995-05-05 1999-06-01 The Scripps Research Institute Treatment of viscous mucous-associated diseases
US5635161A (en) * 1995-06-07 1997-06-03 Abbott Laboratories Aerosol drug formulations containing vegetable oils
US6258032B1 (en) * 1997-01-29 2001-07-10 William M. Hammesfahr Method of diagnosis and treatment and related compositions and apparatus
AUPN814496A0 (en) * 1996-02-19 1996-03-14 Monash University Dermal penetration enhancer
AU2190697A (en) 1996-04-12 1997-11-07 Flemington Pharmaceutical Corporation Buccal polar spray or capsule
US6271240B1 (en) * 1996-05-06 2001-08-07 David Lew Simon Methods for improved regulation of endogenous dopamine in prolonged treatment of opioid addicted individuals
US5891465A (en) * 1996-05-14 1999-04-06 Biozone Laboratories, Inc. Delivery of biologically active material in a liposomal formulation for administration into the mouth
US5795909A (en) * 1996-05-22 1998-08-18 Neuromedica, Inc. DHA-pharmaceutical agent conjugates of taxanes
US5976573A (en) * 1996-07-03 1999-11-02 Rorer Pharmaceutical Products Inc. Aqueous-based pharmaceutical composition
US6071539A (en) 1996-09-20 2000-06-06 Ethypharm, Sa Effervescent granules and methods for their preparation
ZA9711732B (en) 1996-12-31 1998-12-28 Quadrant Holdings Cambridge Methods and compositions for improvement bioavailability of bioactive agents for mucosal delivery
US5906811A (en) * 1997-06-27 1999-05-25 Thione International, Inc. Intra-oral antioxidant preparations
US20030095927A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030077228A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20030077229A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
US20040136914A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing ondansetron
EP1029536B1 (en) * 1997-10-01 2007-11-28 Novadel Pharma Inc. Buccal non-polar spray
US20030190286A1 (en) * 1997-10-01 2003-10-09 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20050163719A1 (en) * 1997-10-01 2005-07-28 Dugger Harry A.Iii Buccal, polar and non-polar spray containing diazepam
US20040141923A1 (en) 1997-10-01 2004-07-22 Dugger Harry A. Buccal, polar and non-polar spray containing alprazolam
US20030185761A1 (en) * 1997-10-01 2003-10-02 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20030077227A1 (en) * 1997-10-01 2003-04-24 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US20050180923A1 (en) * 1997-10-01 2005-08-18 Dugger Harry A.Iii Buccal, polar and non-polar spray containing testosterone
US7632517B2 (en) * 1997-10-01 2009-12-15 Novadel Pharma Inc. Buccal, polar and non-polar spray containing zolpidem
US20050002867A1 (en) * 1997-10-01 2005-01-06 Novadel Pharma Inc. Buccal, polar and non-polar sprays containing propofol
US20030095926A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20040136915A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing atropine
US20030095925A1 (en) * 1997-10-01 2003-05-22 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders
US20040136913A1 (en) * 1997-10-01 2004-07-15 Dugger Harry A. Buccal, polar and non-polar spray containing sumatriptan
US20030082107A1 (en) * 1997-10-01 2003-05-01 Dugger Harry A. Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer
US6212227B1 (en) * 1997-12-02 2001-04-03 Conexant Systems, Inc. Constant envelope modulation for splitterless DSL transmission
AU766703B2 (en) 1998-11-12 2003-10-23 Frank G Pilkiewicz An inhalation system
US6375975B1 (en) * 1998-12-21 2002-04-23 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary application
GB9908921D0 (en) 1999-04-19 1999-06-16 Britannia Pharmaceuticals Ltd Spray dispenser for opiod antagonists
CO5271697A1 (en) * 2000-01-12 2003-04-30 Pfizer Prod Inc COMPOSITIONS AND PROCEDURES FOR THE TREATMENT OF AFFECTIONS THAT RESPOND TO AN INCREASE OF TESTOSTERONE
SI1280515T1 (en) * 2000-03-09 2007-06-30 Gw Pharma Ltd Pharmaceutical compositions comprising cannabis
EP1267941B1 (en) * 2000-03-28 2005-11-23 Farmarc Nederland B.V. Alprazolam inclusion complexes and pharmaceutical compositions thereof
AU3664102A (en) * 2000-12-01 2002-06-11 Battelle Memorial Institute Method for stabilizing biomolecules in liquid formulations
WO2002094232A1 (en) 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Delivery of antidepressants through an inhalation route
US6981591B2 (en) * 2003-07-31 2006-01-03 Umbra Inc. Case with elastic-secured end cap
US7256454B2 (en) * 2005-07-25 2007-08-14 Freescale Semiconductor, Inc Electronic device including discontinuous storage elements and a process for forming the same

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3338978A1 (en) * 1982-10-29 1984-05-03 Basf Ag, 6700 Ludwigshafen Verapamil and gallopamil and their physiologically tolerated salts for application onto the mucous membranes of the mouth, of the naso-pharyngeal space and of the rectum for absorption
DE3246081A1 (en) * 1982-12-13 1984-06-14 G. Pohl-Boskamp GmbH & Co Chemisch-pharmazeutische Fabrik, 2214 Hohenlockstedt Nitroglycerin spray
WO1990001046A1 (en) * 1988-05-02 1990-02-08 Zila Pharmaceuticals, Inc. Compositions and in situ methods for forming films on body tissue
FR2633933A1 (en) * 1988-07-08 1990-01-12 Egyt Gyogyszervegyeszeti Gyar COMPOSITION FOR AEROSOLS CONTAINING NITROGLYCERIN AS ACTIVE INGREDIENT
US4935243A (en) * 1988-12-19 1990-06-19 Pharmacaps, Inc. Chewable, edible soft gelatin capsule
DE4007705C1 (en) * 1990-03-10 1991-09-26 G. Pohl-Boskamp Gmbh & Co. Chemisch-Pharmazeutische Fabrik, 2214 Hohenlockstedt, De
EP0471161A1 (en) * 1990-08-17 1992-02-19 Schwarz Pharma Ag Spray container containing nitroglycerin in a hydrophilic aqueous composition
DE4038203A1 (en) * 1990-11-30 1992-06-04 Kali Chemie Pharma Gmbh Pharmaceutical spray-prepn. for admin. of nitrate(s) - esp. for treatment of cardiovascular, disorders, asthma, migraine and colic
EP0656206A1 (en) * 1991-06-10 1995-06-07 Schering Corporation Non-chlorofluorocarbon aerosol formulations
WO1995024893A1 (en) * 1994-03-16 1995-09-21 R.P. Scherer Limited Delivery systems for hydrophobic drugs
WO1997038687A1 (en) * 1996-04-12 1997-10-23 Flemington Pharmaceutical Corporation Buccal, non-polar spray for nitroglycerin
WO1997038663A2 (en) * 1996-04-12 1997-10-23 Flemington Pharmaceutical Corporation Buccal, non-polar spray or capsule

Cited By (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9078816B2 (en) 1997-10-01 2015-07-14 Suda Ltd. Buccal, polar and non-polar spray containing ondansetron
US6998110B2 (en) 1997-10-01 2006-02-14 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule
US6977070B2 (en) 1997-10-01 2005-12-20 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
US6969508B2 (en) 1997-10-01 2005-11-29 Novadel Pharma, Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US7687453B2 (en) 1998-02-10 2010-03-30 Generex Pharmaceuticals Incorporated Method for administering insulin to the buccal region
US7070799B1 (en) 1998-02-10 2006-07-04 Generex Pharmaceuticals, Inc. Method for administering insulin to the buccal region
US8642662B2 (en) 1998-12-01 2014-02-04 Sunovion Pharmaceuticals Inc. Methods of using derivatives of (−)-venlafaxine
US9072700B2 (en) 1998-12-01 2015-07-07 Sunovion Pharmaceuticals Inc. Methods of using derivatives of (−)-venlafaxine
US6451286B1 (en) 1998-12-21 2002-09-17 Generex Pharmaceuticals Incorporated Pharmaceutical compositions for buccal and pulmonary administration comprising an alkali metal alkyl sulfate and at least three micelle-forming compounds
US6255294B1 (en) * 1998-12-28 2001-07-03 Allergy Limited Cyanocobalamin (vitamin B12) treatment in allergic disease
US6846495B2 (en) 1999-01-11 2005-01-25 The Procter & Gamble Company Compositions having improved delivery of actives
US8269040B2 (en) 1999-04-06 2012-09-18 Wyeth Llc Derivatives of venlafaxine and methods of preparing and using the same
US6432383B1 (en) 2000-03-30 2002-08-13 Generex Pharmaceuticals Incorporated Method for administering insulin
EP1307243A2 (en) * 2000-05-01 2003-05-07 Aeropharm Technology Incorporated A medicinal aerosol formulation
EP1307243A4 (en) * 2000-05-01 2009-04-29 Aeropharm Technology Inc A medicinal aerosol formulation
EP1360169B2 (en) † 2001-02-12 2017-05-24 Wyeth LLC Succinate salt of o-desmethyl-venlafaxine
US10004684B2 (en) 2001-02-14 2018-06-26 Gw Pharma Limited Pharmaceutical formulations
US8846618B2 (en) 2001-06-28 2014-09-30 Novo Nordisk A/S Stable formulation of modified GLP-1
US7253155B2 (en) 2001-10-05 2007-08-07 Combinatorx, Inc. Combinations for the treatment of immunoinflammatory disorders
US7915265B2 (en) 2001-10-05 2011-03-29 Zalicus Inc. Combinations for the treatment of immunoinflammatory disorders
US7138133B2 (en) 2001-10-10 2006-11-21 The Procter & Gamble Company Orally administered liquid compositions
EP2452675A1 (en) * 2002-08-29 2012-05-16 Novadel Pharma Inc. Buccal spray containing sildenafil
EP2277506A1 (en) * 2002-08-29 2011-01-26 Novadel Pharma Inc. Non-polar buccal spray of a sedative
WO2004019912A2 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar or non-polar spray or capsule containing drugs for treating an infectious disease or cancer
WO2004019910A2 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
WO2004019911A2 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar or non-polar spray or capsule containing drugs for treating endocrine disorders
WO2004019903A1 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs fortreating metabolic disorders
WO2004019904A1 (en) * 2002-08-29 2004-03-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
WO2004035021A3 (en) * 2002-08-29 2004-11-11 Novadel Pharma Inc Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
WO2004043428A3 (en) * 2002-08-29 2004-10-21 Novadel Pharma Inc Buccal, polar and non-polar spray or capsule containing drugs for treating pain
WO2004035021A2 (en) * 2002-08-29 2004-04-29 Novadel Pharma Inc. Buccal polar and non-polar spray or capsule containing drugs for treating disorders of the central nervous system
WO2004019912A3 (en) * 2002-08-29 2004-08-19 Novadel Pharma Inc Buccal, polar or non-polar spray or capsule containing drugs for treating an infectious disease or cancer
WO2004043428A2 (en) * 2002-08-29 2004-05-27 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule containing drugs for treating pain
WO2004019909A3 (en) * 2002-08-29 2004-07-08 Novadel Pharma Inc Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs
WO2004019911A3 (en) * 2002-08-29 2004-07-15 Novadel Pharma Inc Buccal, polar or non-polar spray or capsule containing drugs for treating endocrine disorders
EP2283814A1 (en) * 2002-08-29 2011-02-16 Novadel Pharma Inc. Polar buccal spray of a sedative
EP2283813A1 (en) * 2002-08-29 2011-02-16 Novadel Pharma Inc. Propellant-free polar buccal spray of a sedative
EP2283815A1 (en) * 2002-08-29 2011-02-16 Novadel Pharma Inc. Propellant-free non polar buccal spray of a sedative
WO2004019910A3 (en) * 2002-08-29 2004-07-29 Novadel Pharma Inc Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US7348403B2 (en) 2002-12-09 2008-03-25 The Trustees Of Columbia University In The City Of New York Peptides and methods for deactivation of organophosphorus-based nerve agents and insecticides
EP1444976A1 (en) * 2003-02-10 2004-08-11 Novadel Pharma Inc. Buccal, polar and non-polar spray or capsule
WO2004080382A3 (en) * 2003-03-11 2005-03-24 Sirus Pharmaceuticals Ltd Novel compositions containing fentanyl
US8114959B2 (en) 2003-06-03 2012-02-14 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
US8614181B2 (en) 2003-06-03 2013-12-24 Novo Nordisk A/S Stabilized pharmaceutical peptide compositions
WO2005037949A2 (en) * 2003-10-07 2005-04-28 Chrysalis Technologies Incorporated Aerosol formulations of butalbital, lorazepam, ipratropium, baclofen, morphine and scopolamine
US7410635B2 (en) 2003-10-07 2008-08-12 Philip Morris Usa Inc. Aerosol formulations and aerosol delivery of scopolamine
WO2005037949A3 (en) * 2003-10-07 2006-01-12 Chrysalis Tech Inc Aerosol formulations of butalbital, lorazepam, ipratropium, baclofen, morphine and scopolamine
US8080553B2 (en) 2003-10-15 2011-12-20 Zalicus Inc. Methods and reagents for the treatment of immunoinflammatory disorders
EP3300721A1 (en) * 2003-11-20 2018-04-04 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
US8114833B2 (en) 2003-11-20 2012-02-14 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
WO2005049061A3 (en) * 2003-11-20 2005-10-20 Novo Nordisk As Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
CN113304250A (en) * 2003-11-20 2021-08-27 诺和诺德股份有限公司 Propylene glycol-containing peptide formulations optimized for production and use in injection devices
WO2005049061A2 (en) * 2003-11-20 2005-06-02 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
EP2394656A3 (en) * 2003-11-20 2012-01-18 Novo Nordisk A/S Propylene Glycol-containing peptide formulations which are optimal for production and for use in injection devices
AU2004290862B2 (en) * 2003-11-20 2010-06-03 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
US7658945B2 (en) 2004-02-17 2010-02-09 Transcept Pharmaceuticals, Inc. Compositions for delivering hypnotic agents across the oral mucosa and methods of use thereof
WO2005123043A2 (en) * 2004-06-10 2005-12-29 Duramed Pharmaceuticals, Inc. Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same
WO2005123043A3 (en) * 2004-06-10 2007-01-25 Duramed Pharmaceuticals Inc Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same
US8710181B2 (en) 2004-08-31 2014-04-29 Novo Nordisk A/S Use of tris(hydroxymethyl) aminomethane for the stabilization of peptides, polypeptides and proteins
US8748376B2 (en) 2004-11-12 2014-06-10 Novo Nordisk A/S Stable formulations of peptides
WO2007124869A3 (en) * 2006-05-02 2008-04-17 Bayer Healthcare Ag Liquid pharmaceutical formulation
WO2007124869A2 (en) * 2006-05-02 2007-11-08 Bayer Animal Health Gmbh Liquid pharmaceutical formulation
WO2011064316A2 (en) 2009-11-25 2011-06-03 Paolo Botti Mucosal delivery of peptides
EP2526971A1 (en) 2011-05-25 2012-11-28 ArisGen SA Mucosal delivery of drugs
US11752198B2 (en) 2017-08-24 2023-09-12 Novo Nordisk A/S GLP-1 compositions and uses thereof
WO2020075183A1 (en) 2018-10-08 2020-04-16 Troikaa Pharmaceuticals Limited Oromucosal solutions of zolpidem or pharmaceutically acceptable salts thereof
US11318191B2 (en) 2020-02-18 2022-05-03 Novo Nordisk A/S GLP-1 compositions and uses thereof
CN113009057A (en) * 2020-10-22 2021-06-22 重庆医科大学 Method for detecting neonicotinoid insecticides and metabolites in urine by solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry
CN113009057B (en) * 2020-10-22 2023-11-07 重庆医科大学 Method for detecting neonicotinoid insecticides and metabolites in urine by solid phase extraction-ultra-high performance liquid chromatography-tandem mass spectrometry

Also Published As

Publication number Publication date
EP1029536B1 (en) 2007-11-28
EP1029536A1 (en) 2000-08-23
DE69738333T2 (en) 2008-11-27
US20090118170A1 (en) 2009-05-07
EP1019019A1 (en) 2000-07-19
EP1952802A3 (en) 2009-06-17
EP1952802A2 (en) 2008-08-06
US20030039680A1 (en) 2003-02-27
CA2306024C (en) 2011-04-26
US20030211047A1 (en) 2003-11-13
US20040062716A1 (en) 2004-04-01
AU4894697A (en) 1999-04-23
US20050281753A1 (en) 2005-12-22
EP2042161A1 (en) 2009-04-01
CA2306024A1 (en) 1999-04-08
US6676931B2 (en) 2004-01-13
EP1036561A1 (en) 2000-09-20
ES2293875T3 (en) 2008-04-01
JP2001517689A (en) 2001-10-09
DE69738333D1 (en) 2008-01-10
US6998110B2 (en) 2006-02-14

Similar Documents

Publication Publication Date Title
CA2306024C (en) Buccal, polar and non-polar spray or capsule
US6969508B2 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating pain
US20050025712A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating allergies or asthma
US20030095927A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating muscular and skeletal disorders
US20030095926A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating disorders of the gastrointestinal tract or urinary tract
US20030077228A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating endocrine disorders
US20040136913A1 (en) Buccal, polar and non-polar spray containing sumatriptan
EP1682090A1 (en) Buccal, polar and non-polar spray containing ondansetron
US20050287075A1 (en) Buccal, polar and non-polar spray or capsule containing drugs for treating pain
EP1444976A1 (en) Buccal, polar and non-polar spray or capsule

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2306024

Country of ref document: CA

Ref country code: CA

Ref document number: 2306024

Kind code of ref document: A

Format of ref document f/p: F

NENP Non-entry into the national phase

Ref country code: KR

WWE Wipo information: entry into national phase

Ref document number: 1997911621

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1997911621

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642