|Publication number||USRE33093 E|
|Application number||US 07/272,354|
|Publication date||Oct 17, 1989|
|Filing date||Nov 16, 1988|
|Priority date||Jun 16, 1986|
|Publication number||07272354, 272354, US RE33093 E, US RE33093E, US-E-RE33093, USRE33093 E, USRE33093E|
|Inventors||Michael T. Schiraldi, Martin M. Perl, Howard Rubin|
|Original Assignee||Johnson & Johnson Consumer Products, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (3), Referenced by (250), Classifications (6), Legal Events (3)|
|External Links: USPTO, USPTO Assignment, Espacenet|
______________________________________ Outer Protective Bio- % w/w Barrier adhesive Reservoir Membrane Layer Layer LayerIngredients (0.1 mm) (0.025 mm) (0.025 mm)______________________________________Polyethylene oxide 60.0 -- --homopolymer(MW 3,000,000 minimum)Hydroxypropyl Cellulose 30.0 20.0 24.0(MW 1,000,000)Polyethylene (Low Density) 5.0 -- --Propylene Glycol U.S.P. 3.0 -- --Polyethylene Glycol 2.0 -- --(MW 400)Ethyl Cellulose -- 59.0 69.6Caprylic/Capric -- 5.0 6.0TriglycerideSodium Flouride -- 16.0 0.4 100.0 100.0 100.0______________________________________
1. Field of the Invention
The present invention relates to a controlled-releasing medicament-containing preparation for intra-oral use, and is more especially concerned with such a preparation (and the process of using it) in the form of a very thin extruded thermoplastic film (which can be in single layer or laminated multi-layer form) having at least one bioadhesive layer containing .[.40-95.]..Iadd.20-93.Iaddend.% of a thermoplastic cellulose ether and 5-60% of a homopolymer of ethylene oxide which can adhere to the mucosa of the oral cavity. The extruded film drug delivery system of the present invention, which has incorporated therein the medicament to be dispensed, is so thin and flexible when wet as to be unobtrusive to the patient after it has been properly positioned and placed in the mouth.
2. Description of the Prior Art
Several systems have previously been described which pertain to the delivery of drugs into the oral cavity. These include:
1. Treatment of periodontal disease with tetracycline, chlorhexidine or metronidazole loaded into hollow cellulose acetate fibers. These fibers are packed in the periodontal pockets and provide controlled release of the drug to the infected area.
2. Cast films containing ethyl cellulose/propylene glycol with chlorhexidine or metronidazole for treatment of periodontal disease.
3. An orthodontic appliance with a hydroxyethyl methacrylate/methyl methacrylate copolymer (HEMA/MMA) matrix. Sodium fluoride is incorporated into the HEMA/MMA matrix to provide sustained fluoride release and enhanced anticaries activity. HEMA/MMA with fluoride may also be attached to the tooth in the form of a wafer-like tablet.
4. Silicone/ethyl cellulose/polyethylene glycol films containing sodium fluoride are applied as coatings on orthodontic bands or in chewing gum. Controlled release of fluoride and anticaries activity is claimed. The above systems are discussed in the "The Compendium of Continuing Education" Vol VI, No. 1, January 1985 p. 27-36 review article "Controlled Drug Delivery: A New Means of Treatment of Dental Disease", by J. Max Goodson, D.D.S., Ph.D. of the Forsyth Dental Center. Other systems, described in GB patent application No. 2,042,888 and U.S. Pat. Nos. 4,292,299/4,226,848 (Teijin Ltd., Japan), use combinations of cellulosic and polyacrylate polymers. The preferred materials are hydroxypropyl cellulose ("Klucel") and a copolymer of acrylic acid ("Carbopol") that is administered in the form of thin tablets (discs), granules or powder. Other polymers that might be added are vinyl copolymers, polysaccharides, gelatin and collagen. U.S. Pat. No. 4,517,173 (Nippon Soda Co. Ltd, Japan) uses various celluloses in a multi-layered non-extruded cast film preparation.
Examples of prior art products currently on the market include ointments such as ORABASE* with Benzocaine (Squibb), Kenalog* (Triamcinolone Acetonide) in ORABASE* (Squibb) and Mycostatin* (Nystatin) ointment (Squibb).
The prior art products and delivery systems described above are useful but have the following disadvantages:
Tablets, appliances, hollow fibers are "bulky" in the mouth, are difficult to keep in place and inconvenient to apply.
Ethyl cellulose and/or silicone films do not adhere to mucosal tissue.
Ointments (i.e., ORABASE*) have an unpleasant feel and do not last very long.
Except for ORABASE*, all the foregoing systems require professional application to the tooth or periodontal pockets.
The bioadhesive film of the present invention alleviates many of the above problems. It may be applied easily by the consumer. It has very little or no mouthfeel, it has good adhesion to the mucosal tissues, and provides controlled release of the medicament.
It is an object of this invention to provide an extruded film that is an effective and convenient intra-oral drug delivery system and method for applying and delivering controlled dosages of therapeutic agents into the oral cavity. This technology may also be extended for controlled drug delivery in skin care, gynecological applications, wound care and like uses.
The invention involves a pharmaceutically acceptable controlled-releasing medicament-containing extruded single or multi-layered thin film, capable of adhering to a wet mucous surface, comprising a water soluble or swellable polymer matrix bioadhesive layer which can adhere to a wet mucous surface and which bioadhesive layer consists essentially of .[.40-95.Iadd.20-93.Iaddend.% by weight of hydroxypropyl cellulose 5-60% of a homopolymer of ethylene oxide, 0-10% of a water-insoluble polymer selected from the group consisting of ethyl cellulose, propyl cellulose, polyethylene and polypropylene, and 2-10% of a plasticizer, said film having incorporated therein a pharmaceutically effective amount of said medicament.
The present invention is directed to an extruded single or multi-layered laminated thin (1-10 mils or 0.025-0.25 mm) film, composed of selected water soluble and/or insoluble polymers. Various therapeutic agents are incorporated into the film during manufacture which are useful for treatment of oral disorders (i.e., denture discomfort, caries, periodontal disease, aphthous ulcers, etc.).
The extruded film of the present invention must have at least one bioadhesive layer, but may also have a reservoir layer and/or an outer protective barrier membrane layer. The therapeutic agent may be incorporated into any or all of the layers. When properly formulated and fabricated, these films will adhere to wet mucosal surfaces, provide a protective barrier for injured tissue and deliver controlled/sustained dosages of medication to the infected areas. The film may be designed for localized drug delivery (i.e., the periodontal pocket, an aphthous lesion), or may allow diffusion of the drug into the oral cavity.
An example of a non-localized system would be the delivery of sodium fluoride for caries prevention. A single or laminated film with good adhesion to the tooth or mucosal tissue may be employed in which the fluoride release rates may be controlled by varying film solubilities and/or concentration of fluoride in a multi-layered film.
An example of a localized application of medication would be in the treatment of aphthous lesions. A laminated two layer film with benzocaine incorporated into the adhesive layer would directly contact the injured mucosa. The outer layer would consist of non-soluble/non-adhesive polymers that provide durability, protection and directs the delivery of benzocaine toward the lesion.
The film forming polymers that are useful in this invention are selected from pharmaceutical grade materials, or those that are considered generally regarded as safe (GRAS) as food additives. They include, hydroxypropyl cellulose, and polyethylene oxide homopolymers. Small amounts of other polymers, e.g., polyvinyl ether-maleic acid copolymers and the like may be used in small amounts as well, replacing a small portion of the other polymers. The above materials are either water soluble of swellable and are most useful in the bioadhesive layer of the film. Various non-soluble polymers may also be incorporated for modification of the film's permeability properties, such as ethyl cellulose, propyl cellulose, polyethylene, polypropylene and carboxymethylcellulose (free acid). By varying the ratios of the above polymers both the solubility and the adhesive properties of each layer of film may be controlled. Therefore, depending on the desired delivery rate, the type of disorder to be treated, the area to be treated and the medication being administered it is possible to custom design the film by selecting and blending various polymers. The final film product may also be fabricated into flexible tapes of varied thickness and width, "spots" of different sizes and shapes or other pre-shaped forms.
The medicaments and pharmaceutical agents set forth in the prior art discussed above may generally be delivered by the drug delivery system of the present invention. Usable medicaments are those which are capable of withstanding the heats and pressures generated in the extrusion process involved in making the film of the present invention. Preferred medicaments include:
Anesthetics/Analgesics-benzocaine, dyclonine HCl, phenol, aspirin, phenacetin, acetaminophen, potassium nitrate, etc.
Anticaries Agents-sodium fluoride, sodium monofluorophosphate, stannous fluoride, etc.
Anti-inflammatories-hydrocortisone acetate, triamcinolone acetonide, dipotassium, glycyrrhizinate, etc.
Antihistamines-chlorpheniramine maleate, ephedrine HCL, diphenhydramine HCL, etc.
Antibiotics-i.e., tetracycline, doxycycline hyclate, meclocycline, minocycline, etc.
Antibacterials-chlorhexidine, cetyl pyridinium chloride, benzethonium chloride, dequalinium chloride, silver sulfadiazene, phenol, thymol, hexedine, hexetidine, alexidine, etc.
Fungistats-nystatin, miconazole, ketoconazole, etc.
The above are illustrative examples of therapeutic agents that are used to treat oral disorders. The present invention is not to be limited to these specific materials especially where it is intended to deliver drug outside of the oral cavity e.g. to skin where other drugs may be desirable.
The film of the present invention has the advantage of being an extruded film, rather than a cast film. When a multi-layered film is involved, the different layers can be coextruded and then laminated together, or else each layer can be separately extruded one on the other, and then laminated together, so that the final multi-layered film is still very thin. The films of the present invention can be made in thicknesses of only 1-10 mils or 0.025-0.25 mm. The films are so thin that when placed in the mouth after they become wet they soon become unobtrusive, and hardly noticeable by most patients.
The film must always have a bioadhesive layer, which enables it to adhere to wet mucosal surfaces. The bioadhesive layer has .[.40-95.Iadd.20-93.Iaddend.% of hydroxypropyl cellulose, 5-60% of a homopolymer of ethylene oxide and 2-10% of a glycol plasticizer (all percents are % by weight).
The Hydroxypropyl cellulose (HPC), useful for purposes of the present invention is commercially available from Hercules, Inc. (Wilmington, DE) under the tradename KLUCEL*. Preferred grades include Klucel MF, with a molecular weight around 600,000 and having a viscosity of 4,000-6,000 cps (Brookfield) in 2 percent water solutions, or Klucel HF, having a molecular weight around 1,000,000 and viscosity of 1500-2500 cps in 1 percent water solution. In general, any HPC having a Molecular Weight above about 100,000 is useful for purposes of this invention.
The homopolymer of ethylene oxide useful for purposes of the present invention has a relatively high molecular weight, i.e., above 100,000 and preferably above 3,000,000. Such polymers are commercially available from various sources. The Union Carbide Corporation material, "Polyox WSR-301", which has a molecular weight of approximately 4,000,000-5,000,000 is most preferred for purposes of the present invention.
The "plasticizer" useful for purposes of the present invention are selected from glycols such as propylene glycol and polyethylene glycol; polyhydric alcohols such as glycerin and sorbitol; glycerol esters such as glycerol triacetate; fatty acid triglycerides such as NEOBEE* M-5 and MYVEROLS*; mineral oil; vegetable oils such as castor oil, etc.
For the uses for the present invention contemplated here, the plasticizer should be non-toxic. The purpose of the plasticizer is to improve polymer melt processing by reducing the polymer melt viscosity and to impart flexibility to the final product.
The preferred plasticizer for use in the present invention is either propylene glycol or polyethylene glycol (such as is available from Union Carbide Corporation as their series of Carbowaxes which runs from 200 to 600 molecular weight, of which we prefer to use Carbowax 400, which has a molecular weight of 400, average.
In addition to the polymers and plasticizer which are required ingredients of the films of the present invention, minor amounts of other non-essential but customary ingredients will often be used if desired, e.g., antioxidants, preservatives, flavors, colorants.
The following examples will serve to illustrate the present invention in greater detail. The units shown in the examples are parts by weight. The thickness of the layers is expressed in either mils (0.001 inches) or millimeters. For easy conversion, 4 mils is approximately equal to 0.1 mm.
Triple Layered Laminate Containing Sodium Fluoride for Anticaries Protection
This three layered film laminate is comprised of a "bioadhesive" layer, a sodium fluoride "reservoir" layer and, an "outer protective barrier membrane" layer, in which the composition and thickness of each layer are as shown below:
______________________________________ Outer Protective Bio- % w/w Barrier adhesive Reservoir Membrane Layer Layer Layer (4 mils) (1 mil) (1 mil)Ingredients (0.1 mm) (0.025 mm) (0.025 mm)______________________________________Polyethylene oxide 60.0 -- --homopolymer (UnisonCarbide-Polyox* WSR-301)Hydroxypropyl Cellulose 30.0 20.0 24.0(Hercules, Inc.-Klucel* MF)Polyethylene (Allied 5.0 -- --Chemical-6A)(Low Density)Propylene Glycol, U.S.P. 3.0 -- --Polyethylene Glycol 2.0 -- --400 (Union Carbide)Ethyl Cellulose (Hercules, -- 59.0 69.6Inc.-N100F)Caprylic/Capric -- 5.0 6.0Triglyceride(PVOIncorporated-Neobee M-5)Sodium Fluoride, U.S.P. -- 16.0 0.4 100.0 100.0 100.0______________________________________
The process used to make the above laminate was:
a. Powder Blending-Each layer is made separately and all ingredients used therein except propylene glycol and Neobee M-5 (liquid plasticizers) are placed in a Patterson Kelley (PK) V-blender equipped with liquid addition capabilities. The ingredients which are all powders are blended for approximately 10-15 minutes while the liquid plasticizer is slowly added to the mix. Three separate powder blends are made, one for each layer.
b. Extrusion Process-A standard Johnson 2-1/2 inch vinyl/polyolefin extruder equipped with a single three stage screw was used to extrude the "powder blend". The temperature conditions for the water soluble powders are however quite different from those used for vinyls and polyolefins. The temperature (°C.) profile for the "reservoir" and "membrane layers" of the triple laminate was as follows:
______________________________________ Barrel Zone 1 100 Barrel Zone 2 125 Barrel Zone 3 135 Barrel Zone 4 145 Barrel Zone 5 160 Barrel Zone 6 170 Adapter 180 Die Zone 1 180 Die Zone 2 180 Die Zone 3 180______________________________________
The films which had a width of 18 inches, were extruded at approximately 20 feet/minute through a flat lipped die. The temperature profile for the "bioadhesive layer" was:
______________________________________ Barrel Zone 1 125 Barrel Zone 2 140 Barrel Zone 3 165 Barrel Zone 4 170 Barrel Zone 5 185 Barrel Zone 6 185 Adapter 185 Die Zone 1 185 Die Zone 2 185 Die Zone 3 185______________________________________
Each layer is extruded separately with the first layer extruded as a "free film". Successive layers are extruded onto each other and laminated by passing them through heated stainless steel rollers.
In vitro fluoride ion release studies were conducted on samples of the above described triple laminate film measuring 0.5 cm×1.25 cm (0.625 cm2) according to the following procedures:
The test sample is adhered to a glass slide by prewetting the film and placing the bioadhesive layer on the glass surface. The slide is then immersed in a beaker containing 100 ml of distilled water with continuous stirring. Five milliliter aliquots are withdrawn from the solution, at prescribed time intervals, and analyzed for fluoride content with an Orion Ionanalyzer equipped with a fluoride specific electrode. Release rates are then calculated from the data.
The results obtained indicated fluoride release rates in the order of 0.05-0.2 mgs/cm2 /hr for 24 hours. This falls within the desired range for maintaining constant low levels of fluoride in the mouth and enhanced anticaries activity. Release rates may be tailored to desired use levels by modification of the film composition and construction.
Single Layer Adhesive Film Containing Hydrocortisone Acetate (0.5%) As An Anti-Inflammatory Agent
The composition of the film, which was 0.1 mm. thick, was as follows:
______________________________________Ingredients % w/w______________________________________Ethylene Oxide Homopolymer 59.4(Polyox* WSR-301)Hydroxypropyl Cellulose 30.0(Klucel* MF)Polyethylene (AC-6A) 5.0Propylene Glycol 3.0Polyethylene Glycol 400 2.0Butylated Hydroxy Toluene (BHT) 0.1FCC (preservative)Hydrocortisone Acetate 0.5 100.0______________________________________
The powder blending process and extruder conditions used were the same as those described in Example I for the "bioadhesive layer" of the sodium fluoride trilaminate. In vitro tests were performed on the above film and demonstrated a prolonged drug release pattern.
Single Layer Adhesive Film Containing Triamcinolone Acetonide (0.1%) As An Anti-Inflammatory
The composition of the film, which was 0.1 mm. thick, was as follows:
______________________________________Ingredients % w/w______________________________________Ethylene Oxide Homopolymer 59.9(Polyox WSR-301)Hydroxypropyl Cellulose 29.9(Klucel MF)Polyethylene (AC-6A) 5.0Propylene Glycol 3.0Polyethylene Glycol 400 2.0BHT 0.1Triamcinolone Acetonide 0.1 100.0______________________________________
The powder blending process and extruder conditions used to make the film of this Example 3 were the same as those of the "bioadhesive layer" of Example I.
Other desired active medicament ingredients may be incorporated into the adhesive films of any of Examples 1-3 in place of the particular medicament used in said examples. These include Benzocaine (analgesic), Potassium nitrate (analgesic), Silver sulfadiazene (antimicrobial),
Chlorhexidine (antimicrobial), miconazole nitrate (antifungal), Benzethonium chloride (antimicrobial), Tetracycline (antibiotic) and other similar therapeutic compounds.
Analgesic Films with Potassium Nitrate
This example shows 5 variations of the film having different solubilities, resulting in different release rates.
______________________________________ % w/wIngredients 1 2 3 4 5______________________________________Polyethylene oxide 23.75 57.00 55.00 55.00 57.00homopolymer (Polyox*WSR-301)Hydroxypropyl Cell- 68.30 -- -- -- --ulose, N.F. (Klucel* HF)Hydroxypropyl Cell- -- 28.40 29.90 22.40 22.40ulose, N.F. (Klucel* MF)Ethyl Cellulose -- 4.75 5.00 12.50 12.50Polyethylene Glycol 400 1.90 1.90 2.00 2.00 2.00Polyethylene Glycol 8000 0.95 -- -- -- --Propylene Glycol, U.S.P. -- 2.85 3.00 3.00 3.00BHT, F.C.C. 0.10 0.10 0.10 0.10 0.10Potassium Nitrate, F.C.C. 5.00 5.00 5.00 5.00 3.00______________________________________
The above ingredients are blended in a Patterson-Kelly powder blender equipped with liquid addition capabilities. The resulting powder blend is then extruded into film on a Killion or Johnson vinyl extruder using processing procedures similar to those of the bioadhesive layer of Example I.
Anesthetic Films with Benzocaine (Laminate)
This is an example of a two-layer laminate. The processing conditions used were similar to those of the bioadhesive layer and outer protective barrier membrane layer of Example I.
______________________________________A. Inner medicated bioadhesive layer Polyoxyethylene Homopolymer 57.00 (Polyox* WSR-301) Hydroxypropyl Cellulose, N.F. 28.40 (Klucel* MF) Polyethylene (AC-6A) 4.75 Propylene Glycol, U.S.P. 2.85 Polyethylene Glycol 400 1.90 BHT, F.C.C. 0.10 Benzocaine, U.S.P. 5.00 100.00B. Outer protective/barrier layer Hydroxypropyl Cellulose 78.00 (Klucel* MF) Ethyl Cellulose 20.00 Polyethylene Glycol 400 2.00 100.00______________________________________
Part A was extruded on a Johnson extruder followed by subsequent extrusion and lamination of Part B to A.
Samples were applied to oral lesions, and provided profound anesthetic effects (lasting several hours) within minutes of application.
The identical two-layer laminate may also be made by coextruding the inner medicated bioadhesive layer (Part A) and the outer protective barrier layer (Part B) through separate die slots within a coextruder and laminating the two layers together.
Anesthetic Films with Phenol and Dyclonine HCl
Four variations of a single layer bioadhesive film were made as shown below:
______________________________________Ingredients 1 2 3 4______________________________________Polyethylene oxide homo- 59.10 54.00 59.70 58.20polymer (Polyox* WSR-301)Hydroxypropyl Cellulose 29.45 26.91 29.75 29.00(Klucel HF)Ethyl Cellulose 4.93 4.50 4.98 4.85Propylene Glycol, U.S.P. 2.96 2.70 2.99 2.91Polyethylene Glycol 400 1.97 1.80 1.99 1.94BHT, F.C.C. 0.09 0.09 0.09 0.10Phenol, U.S.P. 1.50 -- -- --Dyclonine HCl -- 10.00 0.50 3.00______________________________________
Following the procedures for the bioadhesive layer of Example I, the powders were blended in P-K blender equipped with liquid addition capabilities. Resulting powders were extruded on a Killion laboratory-sized extruder.
Silver Sulfadiazene Films-Antimicrobial
Three different single-layered bioadhesive films containing 1.0% 0.5% and 0.5% respectively of silver sulfadiazene (SSD) were prepared on a heated Carver laboratory press (designed to simulate extruded conditions) as shown below.
______________________________________ % w/wIngredients A B______________________________________Polyethylene oxide homopolymer 60.00 60.00(Polyox* WSR-301)Hydroxypropyl Cellulose 28.9 29.4(Klucel* HF)Polyethylene (AC-6A) 5.0 5.0Propylene Glycol, U.S.P. 3.0 3.0Polyethylene Glycol 400 2.0 2.0BHT, F.C.C. 0.1 0.1Silver Sulfadiazine 1.0 0.5 100.0 100.0______________________________________
Effects on wound repair and activity against Staphylococcus aureus were evaluated in the guinea pig model. Full-thickness excisions were inoculated with 3.8×105 organisms, (Staph. aureus) and wound surface microbiology samples taken 10 minutes and 24 hours after treatment. Test films were placed on the wound and covered with BIOCLUSIVE* Transparent Dressings secured with elastic tape. Wound contraction was measured over an eight-day period using OPTOMAX* Computer-Assisted Image Analysis. The three films tested were the following:
A. 1.0% Silver Sulfadiazene, 125° C./2 minutes/4 tons
B. 0.5% Silver Sulfadiazene, 125° C./2 minutes/4 tons
C. 0.5% Silver Sulfadiazene, 150° C./3 minutes/4 tons
SILVADENE Cream and an untreated occluded control. The results indicated that:
1. SILVADENE* treated wounds significantly inhibited full-thickness wound contraction.
2. Film A, B and C inhibited wound contraction relative to that of BIOCLUSIVE* dressed wounds.
3. The three SSD films each permitted substantially faster wound contraction than that of wounds treated daily with SILVADENE* cream.
4. All films were very active against S. Aureus 24 hours after inoculation.
The films may be scaled up by using an extruder. This example demonstrates the feasibility of such a film to perform its intended purpose. Use of a press for larger samples would result in a non-uniform and lower-quality film than an extruded film.
Based on the above findings, the films were very effective antibacterial agents, while mildly inhibiting wound contraction. They offer clinicians a convenient and more effective delivery system for antimicrobials which can be place in wounds beneath any dressing or can be laminated to any acceptable dressing face.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US4292299 *||Jul 7, 1980||Sep 29, 1981||Teijin Limited||Slow-releasing medical preparation to be administered by adhering to a wet mucous surface|
|US4421738 *||Mar 18, 1982||Dec 20, 1983||Eisai Co., Ltd.||Sugar-coated tablet containing fat-soluble pharmaceutical material|
|US4517173 *||Sep 25, 1981||May 14, 1985||Nippon Soda Co. Ltd.||Mucous membrane-adhering film preparation and process for its preparation|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US4997830 *||Feb 7, 1990||Mar 5, 1991||The Research Foundation Of State University Of New York||Pharmaceutical composition for the treatment of periodontitis|
|US5064650 *||Apr 4, 1989||Nov 12, 1991||Southwest Research Institute||Controlled-release salt sensitive capsule for oral use and adhesive system|
|US5112620 *||Sep 20, 1990||May 12, 1992||Mikkur, Inc.||Polyethylene glycol ointment for apthous ulcers|
|US5114718 *||Sep 20, 1990||May 19, 1992||The Procter & Gamble Company||Sustained release compositions for treating periodontol disease|
|US5133971 *||Oct 2, 1990||Jul 28, 1992||Phoebe Copelan||Personal dental hygiene assembly|
|US5135752 *||Oct 14, 1988||Aug 4, 1992||Zetachron, Inc.||Buccal dosage form|
|US5155144 *||Oct 29, 1990||Oct 13, 1992||Manganaro James L||Polysaccharide-based porous sheets|
|US5262164 *||Nov 17, 1989||Nov 16, 1993||The Procter & Gamble Company||Sustained release compositions for treating periodontal disease|
|US5288532 *||Oct 27, 1992||Feb 22, 1994||Viskase Corporation||Transferable modifier-containing film|
|US5364634 *||Nov 8, 1991||Nov 15, 1994||Southwest Research Institute||Controlled-release PH sensitive capsule and adhesive system and method|
|US5374457 *||Oct 1, 1993||Dec 20, 1994||Viskase Corporation||Transferable modifier-containing film|
|US5382391 *||Sep 23, 1993||Jan 17, 1995||Viskase Corporation||Method for producing transferable modifier-containing film|
|US5447725 *||Jun 11, 1993||Sep 5, 1995||The Procter & Gamble Company||Methods for aiding periodontal tissue regeneration|
|US5700478 *||Aug 19, 1994||Dec 23, 1997||Cygnus, Inc.||Water-soluble pressure-sensitive mucoadhesive and devices provided therewith for emplacement in a mucosa-lined body cavity|
|US5714165 *||Apr 1, 1992||Feb 3, 1998||Mikkur, Inc.||Bioadhesive polyethylene glycol ointment for medicaments|
|US5851551 *||Jun 21, 1994||Dec 22, 1998||The Gillette Company||Sustained-release matrices for dental application|
|US5894017 *||Jun 6, 1997||Apr 13, 1999||The Procter & Gamble Company||Delivery system for an oral care substance using a strip of material having low flexural stiffness|
|US5906814 *||Oct 22, 1996||May 25, 1999||The Andrew Jergens Company||Topical film-forming compositions|
|US5906834 *||Oct 9, 1996||May 25, 1999||The Gillette Company||Color changing matrix as wear indicator|
|US5958452||Apr 10, 1997||Sep 28, 1999||Euro-Celtique, S.A.||Extruded orally administrable opioid formulations|
|US5965161||Nov 4, 1994||Oct 12, 1999||Euro-Celtique, S.A.||Extruded multi-particulates|
|US5998431||Apr 16, 1998||Dec 7, 1999||Gillette Canada Inc.||Sustained-release matrices for dental application|
|US6068855||Nov 3, 1995||May 30, 2000||Euro-Celtique S. A.||Pharmaceutical composition containing a fusible carrier and method for producing the same|
|US6231957||May 6, 1999||May 15, 2001||Horst G. Zerbe||Rapidly disintegrating flavor wafer for flavor enrichment|
|US6261599||Jul 23, 1999||Jul 17, 2001||Euro-Celtique, S.A.||Melt-extruded orally administrable opioid formulations|
|US6335033||Jul 22, 1999||Jan 1, 2002||Euro-Celtique, S.A.||Melt-extrusion multiparticulates|
|US6375963||Jun 15, 2000||Apr 23, 2002||Michael A. Repka||Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof|
|US6419906 *||Mar 12, 2001||Jul 16, 2002||Colgate Palmolive Company||Strip for whitening tooth surfaces|
|US6503486 *||Feb 22, 2002||Jan 7, 2003||Colgate Palmolive Company||Strip for whitening tooth surfaces|
|US6514483 *||Feb 22, 2002||Feb 4, 2003||Colgate Palmolive Company||Strip for whitening tooth surfaces|
|US6551579||May 29, 2001||Apr 22, 2003||The Procter & Gamble Company||Delivery systems for a tooth whitener|
|US6562363||Sep 28, 1998||May 13, 2003||Noven Pharmaceuticals, Inc.||Bioadhesive compositions and methods for topical administration of active agents|
|US6566350 *||May 21, 2001||May 20, 2003||Showa Yakuhin Kako Co., Ltd.||Minocycline-containing compositions|
|US6582708||Jun 28, 2000||Jun 24, 2003||The Procter & Gamble Company||Tooth whitening substance|
|US6638881||Dec 22, 2000||Oct 28, 2003||Combe Incorporated||Dental adhesive device and method of producing same|
|US6660292||Jun 19, 2001||Dec 9, 2003||Hf Flavoring Technology Llp||Rapidly disintegrating flavored film for precooked foods|
|US6682721||Feb 13, 2001||Jan 27, 2004||Lg Household & Healthcare Ltd.||Patches for teeth whitening|
|US6689344||Sep 13, 2002||Feb 10, 2004||Lg Household & Healthcare Ltd.||Patches for teeth whitening|
|US6706281||Jan 2, 2002||Mar 16, 2004||Euro-Celtique, S.A.||Melt-extrusion multiparticulates|
|US6743442||Feb 6, 2001||Jun 1, 2004||Euro-Celtique, S.A.||Melt-extruded orally administrable opioid formulations|
|US6780401||May 27, 2003||Aug 24, 2004||Lg Household & Healthcare Ltd.||Patches for teeth whitening|
|US6860736||Feb 19, 2004||Mar 1, 2005||Ultradent Products, Inc.||Oral treatment devices that include a thin, flexible barrier layer and an endoskeleton treatment or adhesive composition|
|US6884426||Dec 17, 2002||Apr 26, 2005||The Procter & Gamble Co.||Methods for whitening teeth|
|US6946142||Jun 20, 2002||Sep 20, 2005||Lg Household & Healthcare Ltd.||Multi-layer patches for teeth whitening|
|US6949240||May 23, 2002||Sep 27, 2005||The Procter & Gamble Company||Tooth whitening products|
|US6964571||Nov 4, 2003||Nov 15, 2005||Ultradent Products, Inc.||Pre-shaped dental trays and treatment devices and methods that utilize such dental trays|
|US6981874||Feb 19, 2004||Jan 3, 2006||Ultradent Products, Inc.||Dental bleaching compositions and devices having a solid activation adhesive layer or region and bleaching gel layer or region|
|US6997708||Dec 5, 2003||Feb 14, 2006||Ultradent Products, Inc.||Treatment compositions and strips having a solid adhesive layer and treatment gel adjacent thereto|
|US7004756||Jan 24, 2003||Feb 28, 2006||Ultradent Products, Inc.||Pre-shaped dental trays and treatment devices and methods that utilize such dental trays|
|US7011523||Oct 22, 2003||Mar 14, 2006||Ultradent Products, Inc.||Bleaching compositions and devices having a solid adhesive layer and bleaching gel adjacent thereto|
|US7018622||Oct 24, 2002||Mar 28, 2006||The Procter & Gamble Company||Structures and compositions increasing the stability of peroxide actives|
|US7040897||May 23, 2003||May 9, 2006||Ultradent Products, Inc.||Thin, flexible membrane dental trays and systems and methods utilizing such trays|
|US7048543||May 27, 2003||May 23, 2006||Ultradent Products, Inc.||Substantially solid bleaching composition in a tray-like configuration|
|US7052275||Aug 22, 2003||May 30, 2006||Ultradent Products, Inc.||Kits and methods for bleaching and desensitizing teeth|
|US7056118||Aug 22, 2003||Jun 6, 2006||Ultradent Products, Inc.||Compositions and devices having a tray-like configuration for delivering a medicament and methods of manufacturing and using such compositions and devices|
|US7059857||Aug 8, 2003||Jun 13, 2006||Ultradent Products, Inc.||Substantially solid desensitizing compositions and devices having a tray-like configuration and methods of manufacturing and using such compositions and devices|
|US7059858||Feb 19, 2004||Jun 13, 2006||Ultradent Products, Inc.||Universal tray design having anatomical features to enhance fit|
|US7074042||May 27, 2003||Jul 11, 2006||Ultradent Products, Inc.||Tray-like dental bleaching devices having a barrier layer and a substantially solid bleaching composition|
|US7122199||Apr 6, 2005||Oct 17, 2006||The Procter & Gamble Company||Methods for whitening teeth|
|US7132113||Apr 16, 2002||Nov 7, 2006||Intelgenx Corp.||Flavored film|
|US7192280||Feb 19, 2004||Mar 20, 2007||Ultradent Products, Inc.||Dental bleaching devices having a protective adhesive region|
|US7247022||Jan 31, 2005||Jul 24, 2007||Ultradent Products, Inc.||Dental tray system with releasable hold inner and outer dental trays|
|US7264471||May 5, 2004||Sep 4, 2007||Ultradent Products, Inc.||Methods and kits for bleaching teeth while protecting adjacent gingival tissue|
|US7338664||Sep 15, 2003||Mar 4, 2008||The Gillette Company||Color changing matrix as wear indicator|
|US7357891||Jan 30, 2004||Apr 15, 2008||Monosol Rx, Llc||Process for making an ingestible film|
|US7425292||Feb 14, 2002||Sep 16, 2008||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US7452209||May 2, 2005||Nov 18, 2008||Ultradent Products, Inc.||Exoskeleton support for placement of a dental treatment strip|
|US7470397||Oct 22, 2004||Dec 30, 2008||Adhesives Research, Inc.||Disintegratable films for diagnostic devices|
|US7481653||Feb 9, 2005||Jan 27, 2009||Oratech Lc||Preshaped thin-walled dental trays and methods of manufacturing and using such trays|
|US7510727||Dec 23, 2003||Mar 31, 2009||Purdue Pharma L.P.||Melt-extrusion multiparticulates|
|US7576067||Dec 1, 2004||Aug 18, 2009||Isis Pharmaceuticals, Inc.||Pulsatile release compositions and methods for enhanced intestinal oligonucleotide drug absorption|
|US7625210||Aug 9, 2004||Dec 1, 2009||Ultradent Products, Inc.||Treatment devices for providing oral treatments and kits and methods that utilize such treatment devices|
|US7666337||May 28, 2004||Feb 23, 2010||Monosol Rx, Llc||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US7727466||Nov 21, 2008||Jun 1, 2010||Adhesives Research, Inc.||Disintegratable films for diagnostic devices|
|US7766658||Nov 30, 2004||Aug 3, 2010||Align Technology, Inc.||Systems and methods for intra-oral diagnosis|
|US7785572||May 28, 2004||Aug 31, 2010||Lg Household And Health Care Ltd.||Method and device for teeth whitening using a dry type adhesive|
|US7824588||Apr 14, 2008||Nov 2, 2010||Monosol Rx, Llc||Method of making self-supporting therapeutic active-containing film|
|US7862802||Aug 10, 2004||Jan 4, 2011||Lg Household & Health Care Ltd.||Patches for teeth whitening|
|US7910641||Dec 14, 2006||Mar 22, 2011||Monosol Rx, Llc||PH modulated films for delivery of actives|
|US7947508||Oct 31, 2007||May 24, 2011||Align Technology, Inc.||Systems and methods for intra-oral diagnosis|
|US7972618||Sep 20, 2007||Jul 5, 2011||Monosol Rx, Llc||Edible water-soluble film containing a foam reducing flavoring agent|
|US8007277||Aug 9, 2007||Aug 30, 2011||Ultradent Products, Inc.||Non-custom dental treatment trays and mouth guards having improved anatomical features|
|US8017150||Apr 22, 2008||Sep 13, 2011||Monosol Rx, Llc||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US8049426||Aug 8, 2008||Nov 1, 2011||Tessera, Inc.||Electrostatic fluid accelerator for controlling a fluid flow|
|US8075309||Oct 31, 2007||Dec 13, 2011||Align Technology, Inc.||Systems and methods for intra-oral drug delivery|
|US8075872||Feb 6, 2006||Dec 13, 2011||Gruenenthal Gmbh||Abuse-proofed dosage form|
|US8114383||Nov 20, 2003||Feb 14, 2012||Gruenenthal Gmbh||Abuse-proofed dosage form|
|US8114384||Jul 14, 2004||Feb 14, 2012||Gruenenthal Gmbh||Process for the production of an abuse-proofed solid dosage form|
|US8173152||Mar 22, 2007||May 8, 2012||Auxilium Us Holdings, Llc||Stabilized compositions containing alkaline labile drugs|
|US8192722||Jun 17, 2008||Jun 5, 2012||Grunenthal Gmbh||Abuse-proof dosage form|
|US8202091||Aug 29, 2008||Jun 19, 2012||Ultradent Products, Inc.||Dental treatment trays comprising silicone elastomeric material|
|US8277215||Jun 5, 2006||Oct 2, 2012||Ultradent Products, Inc.||Universal non-custom dental tray having anatomical features to enhance fit|
|US8282954||Dec 15, 2008||Oct 9, 2012||Monosol Rx, Llc||Method for manufacturing edible film|
|US8309060||Jan 9, 2012||Nov 13, 2012||Grunenthal Gmbh||Abuse-proofed dosage form|
|US8323889||Jun 17, 2008||Dec 4, 2012||Gruenenthal Gmbh||Process for the production of an abuse-proofed solid dosage form|
|US8383152||Jan 23, 2009||Feb 26, 2013||Gruenenthal Gmbh||Pharmaceutical dosage form|
|US8420056||Oct 11, 2011||Apr 16, 2013||Grunenthal Gmbh||Abuse-proofed dosage form|
|US8439674||Dec 13, 2011||May 14, 2013||Align Technology, Inc.||Systems and methods for intra-oral drug delivery|
|US8444413||Aug 29, 2011||May 21, 2013||Ultradent Products, Inc.||Non-custom dental treatment trays having improved anatomical features|
|US8465759||Mar 22, 2007||Jun 18, 2013||Auxilium Us Holdings, Llc||Process for the preparation of a hot-melt extruded laminate|
|US8475832||Aug 7, 2009||Jul 2, 2013||Rb Pharmaceuticals Limited||Sublingual and buccal film compositions|
|US8557286||Apr 20, 2000||Oct 15, 2013||Euroceltique, S.A.||Method for producing a water-insoluble amorphous or partially amorphous controlled release matrix|
|US8603514||Jul 10, 2007||Dec 10, 2013||Monosol Rx, Llc||Uniform films for rapid dissolve dosage form incorporating taste-masking compositions|
|US8613285||Apr 9, 2010||Dec 24, 2013||Philip Morris Products S.A.||Extrudable and extruded compositions for delivery of bioactive agents, method of making same and method of using same|
|US8647314 *||Feb 27, 2009||Feb 11, 2014||Lts Lohmann Therapie-Systeme Ag||Gingival wafer|
|US8647607||Apr 28, 2006||Feb 11, 2014||Lg Household & Health Care Ltd.||Patches for teeth whitening|
|US8652378||Mar 29, 2013||Feb 18, 2014||Monosol Rx Llc||Uniform films for rapid dissolve dosage form incorporating taste-masking compositions|
|US8652446||Nov 19, 2003||Feb 18, 2014||Lg Household & Healthcare Ltd.||Apparatus and method for whitening teeth|
|US8663687||May 13, 2010||Mar 4, 2014||Monosol Rx, Llc||Film compositions for delivery of actives|
|US8663696||Aug 17, 2012||Mar 4, 2014||Monosol Rx, Llc||Film delivery system for tetrahydrolipstatin|
|US8685437||Mar 26, 2009||Apr 1, 2014||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US8721332||Jan 15, 2013||May 13, 2014||Ultradent Products, Inc.||Non-custom dental treatment trays having improved anatomical features|
|US8722086||Mar 7, 2008||May 13, 2014||Gruenenthal Gmbh||Dosage form with impeded abuse|
|US8765167||Sep 8, 2006||Jul 1, 2014||Monosol Rx, Llc||Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions|
|US8815289||May 23, 2013||Aug 26, 2014||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US8821929||May 23, 2013||Sep 2, 2014||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US8834925||May 23, 2013||Sep 16, 2014||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US8846086||May 23, 2013||Sep 30, 2014||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US8883187||May 3, 2012||Nov 11, 2014||Auxilium Us Holdings, Llc||Stabilized compositions containing alkaline labile drugs|
|US8894987||Aug 24, 2007||Nov 25, 2014||William H. McKenna||Tamper resistant dosage forms|
|US8894988||May 23, 2013||Nov 25, 2014||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US8900497||Aug 23, 2013||Dec 2, 2014||Monosol Rx, Llc||Process for making a film having a substantially uniform distribution of components|
|US8900498||Aug 23, 2013||Dec 2, 2014||Monosol Rx, Llc||Process for manufacturing a resulting multi-layer pharmaceutical film|
|US8906277||Aug 23, 2013||Dec 9, 2014||Monosol Rx, Llc||Process for manufacturing a resulting pharmaceutical film|
|US8911719||May 23, 2013||Dec 16, 2014||Purdue Pharma Lp||Tamper resistant dosage forms|
|US8944819||Dec 21, 2010||Feb 3, 2015||Ranir, Llc||Device and method for delivering an oral care agent|
|US8956160||Jul 2, 2002||Feb 17, 2015||Ranir, Llc||Device and method for delivering an oral care agent|
|US8974826||Jun 10, 2011||Mar 10, 2015||Monosol Rx, Llc||Nanoparticle film delivery systems|
|US9084816||Oct 16, 2014||Jul 21, 2015||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9095614||Oct 16, 2014||Aug 4, 2015||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9095615||Oct 16, 2014||Aug 4, 2015||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9101661||Oct 16, 2014||Aug 11, 2015||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9108340||Aug 23, 2013||Aug 18, 2015||Monosol Rx, Llc||Process for manufacturing a resulting multi-layer pharmaceutical film|
|US9161917||Nov 1, 2010||Oct 20, 2015||Grünenthal GmbH||Process for the preparation of a solid dosage form, in particular a tablet, for pharmaceutical use and process for the preparation of a precursor for a solid dosage form, in particular a tablet|
|US9198865 *||Nov 17, 2006||Dec 1, 2015||Dow Global Technologies Llc||Biologically active composition comprising ethylcellulose|
|US9364445||Oct 17, 2014||Jun 14, 2016||Auxilium Us Holdings, Llc||Stabilized compositions containing alkaline labile drugs|
|US9486412||Jun 3, 2015||Nov 8, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9486413||Jun 3, 2015||Nov 8, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9492389||Jun 3, 2015||Nov 15, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9492390||Jun 3, 2015||Nov 15, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9492391||Jun 3, 2015||Nov 15, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9492392||Jun 3, 2015||Nov 15, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9492393||Jun 3, 2015||Nov 15, 2016||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9498410||Dec 21, 2007||Nov 22, 2016||Colgate-Palmolive Company||Oral and personal care compositions and methods|
|US9545380||Jun 3, 2015||Jan 17, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9554976||Jul 30, 2013||Jan 31, 2017||The Procter & Gamble Company||Tooth whitening product|
|US9579285||Feb 1, 2011||Feb 28, 2017||Gruenenthal Gmbh||Preparation of a powdery pharmaceutical composition by means of an extruder|
|US9585961||Dec 10, 2012||Mar 7, 2017||Adhesives Research, Inc.||Rapidly disintegrating films for delivery of pharmaceutical or cosmetic agents|
|US9629807||Apr 19, 2016||Apr 25, 2017||Grünenthal GmbH||Abuse-proofed dosage form|
|US9636303||Sep 1, 2011||May 2, 2017||Gruenenthal Gmbh||Tamper resistant dosage form comprising an anionic polymer|
|US9642850||Nov 15, 2016||May 9, 2017||Purdue Pharma L.P.||Method of providing sustained analgesia with buprenorphine|
|US9655853||May 27, 2016||May 23, 2017||Grünenthal GmbH||Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer|
|US9675610||Aug 24, 2016||Jun 13, 2017||Grünenthal GmbH||Abuse-proofed dosage form|
|US9687454||Jan 6, 2016||Jun 27, 2017||Indivior Uk Limited||Sublingual and buccal film compositions|
|US9717577||Oct 7, 2016||Aug 1, 2017||Ultradent Products, Inc.||Non-custom dental tray having anatomical cuspid-bicuspid cuts and/or V or U-shaped indentation in bottom wall|
|US9717682||Jan 23, 2013||Aug 1, 2017||Intelgenx Corporation||Solid oral film dosage forms and methods for making same|
|US9737490||May 27, 2014||Aug 22, 2017||Grünenthal GmbH||Tamper resistant dosage form with bimodal release profile|
|US9750701||Dec 11, 2015||Sep 5, 2017||Grünenthal GmbH||Pharmaceutical dosage form|
|US9763886||Jan 24, 2017||Sep 19, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9763933||Jan 24, 2017||Sep 19, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9770416||Jan 24, 2017||Sep 26, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9770417||Jan 24, 2017||Sep 26, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9775808||Jan 24, 2017||Oct 3, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9775809||Jan 24, 2017||Oct 3, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9775810||Jan 24, 2017||Oct 3, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9775811||Jan 24, 2017||Oct 3, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9775812||Sep 13, 2016||Oct 3, 2017||Purdue Pharma L.P.||Tamper resistant dosage forms|
|US9801837||May 8, 2007||Oct 31, 2017||The University Of Mississippi||Stabilized formulation of triamcinolone acetonide|
|US20030053962 *||Apr 16, 2002||Mar 20, 2003||Zerbe Horst G.||Flavored film|
|US20030059381 *||Oct 24, 2002||Mar 27, 2003||Goodhart Lesle Marie||Structures and compositions increasing the stability of peroxide actives|
|US20030167556 *||Mar 5, 2002||Sep 11, 2003||Consumers Choice Systems, Inc.||Methods and devices for transdermal delivery of anti-aging compounds for treatment and prevention of facial or neck skin aging|
|US20040018241 *||May 13, 2003||Jan 29, 2004||Noven Pharmaceuticals, Inc.||Bioadhesive compositions and methods for topical administration of active agents|
|US20040120991 *||Sep 5, 2003||Jun 24, 2004||Mars Incorporated||Edible films having distinct regions|
|US20040146836 *||Jan 24, 2003||Jul 29, 2004||Andersen Scot N.||Pre-shaped dental trays and treatment devices and methods that utilize such dental trays|
|US20040219111 *||May 28, 2004||Nov 4, 2004||Ji-Young Kim||Method and device for teeth whitening using a dry type adhesive|
|US20040241294 *||May 31, 2003||Dec 2, 2004||Barabolak Roman M.||Edible films including aspartame and methods of making same|
|US20040241615 *||May 27, 2003||Dec 2, 2004||Allred Peter M.||Tray-like dental bleaching devices having a barrier layer and a substantially solid bleaching composition|
|US20040241616 *||May 27, 2003||Dec 2, 2004||Ultradent Products, Inc.||Substantially solid bleaching composition in a tray-like configuration|
|US20040241617 *||Aug 8, 2003||Dec 2, 2004||Allred Peter M.||Substantially solid desensitizing compositions and devices having a tray-like configuration and methods of manufacturing and using such compositions and devices|
|US20040258896 *||Jan 30, 2004||Dec 23, 2004||Monosolrx Llc.||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20050037055 *||May 28, 2004||Feb 17, 2005||Monosolrx Llc.||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US20050089568 *||Sep 16, 2003||Apr 28, 2005||Euro-Celtique S.A.||Melt-extruded orally administrable opioid formulations|
|US20050089820 *||Dec 5, 2003||Apr 28, 2005||Allred Peter M.||Treatment compositions and strips having a solid adhesive layer and treatment gel adjacent thereto|
|US20050100515 *||Sep 8, 2004||May 12, 2005||The Procter & Gamble Company||Tooth whitening products|
|US20050136381 *||Feb 9, 2005||Jun 23, 2005||Andersen Scot N.||Preshaped thin-walled dental trays and methods of manufacturing and using such trays|
|US20050143303 *||Nov 18, 2004||Jun 30, 2005||Nastech Pharmaceutical Company Inc.||Intranasal administration of glucose-regulating peptides|
|US20050186150 *||Feb 19, 2004||Aug 25, 2005||Allred Peter M.||Dental bleaching devices having a protective adhesive region|
|US20050186539 *||Feb 19, 2004||Aug 25, 2005||Mclean Bruce S.||Universal tray design having anatomical features to enhance fit|
|US20050196443 *||Dec 1, 2004||Sep 8, 2005||Isis Pharmaceuticals, Inc.||Pulsatile release compositions and methods for enhanced intestinal drug absorption|
|US20050208108 *||Mar 19, 2004||Sep 22, 2005||Jannusch Leonard C||Thermoplastic films and methods for making|
|US20060057165 *||Sep 9, 2005||Mar 16, 2006||Dimitrios Dimitrakoudis||Clostridium botulinum toxin formulation and method for reducing weight|
|US20060074025 *||Dec 2, 2005||Apr 6, 2006||Nastech Pharmaceutical Company Inc.||Therapeutic formulations for transmucosal administration that increase glucagon-like peptide-1 bioavailability|
|US20060115782 *||Nov 30, 2004||Jun 1, 2006||Chunhua Li||Systems and methods for coating a dental appliance|
|US20060115785 *||Nov 30, 2004||Jun 1, 2006||Chunhua Li||Systems and methods for intra-oral drug delivery|
|US20060116561 *||Nov 30, 2004||Jun 1, 2006||Tricca Robert E||Systems and methods for intra-oral diagnosis|
|US20060171905 *||Jan 31, 2005||Aug 3, 2006||Allred Peter M||Dental bleaching compositions having a protective coating applied thereto|
|US20060172260 *||Jan 31, 2005||Aug 3, 2006||Allred Peter M||Dental tray system with releasable hold inner and outer dental trays|
|US20060193794 *||Apr 28, 2006||Aug 31, 2006||Ji-Young Kim||Patches for teeth whitening|
|US20060207721 *||Mar 17, 2005||Sep 21, 2006||Greg Slominski||Polymer adhesive splicing of water-soluble, orally ingestible thin film webs|
|US20070172515 *||Jan 19, 2007||Jul 26, 2007||Monosolrx, Llc||Film bandage for mucosal administration of actives|
|US20070269388 *||Jul 31, 2007||Nov 22, 2007||The Procter & Gamble Company||Tooth whitening strips|
|US20070269491 *||Jul 31, 2007||Nov 22, 2007||The Procter & Gamble Company||Tooth whitening strips|
|US20070269520 *||Jul 31, 2007||Nov 22, 2007||The Procter & Gamble Company||Tooth whitening strips|
|US20070275023 *||Jul 31, 2007||Nov 29, 2007||The Procter & Gamble Company||Tooth whitening strips|
|US20070298087 *||Jan 18, 2007||Dec 27, 2007||Biegajski James E||Two-phase mucoadhesive composition|
|US20070298380 *||Jun 26, 2006||Dec 27, 2007||Ultradent Products, Inc.||Dental treatment devices adapted for improved lingual side adhesion|
|US20080038211 *||Jul 31, 2007||Feb 14, 2008||Sagel Paul A||Tooth whitening strips|
|US20080075825 *||Sep 20, 2007||Mar 27, 2008||Fuisz Richard C||Edible Water-Soluble Film Containing a Foam Reducing Flavoring Agent|
|US20080119698 *||Oct 31, 2007||May 22, 2008||Tricca Robert E||Systems and methods for intra-oral diagnosis|
|US20080200452 *||Jul 20, 2006||Aug 21, 2008||Petra Obermeier||Oral, Rapidly Disintegrating Film, Which Cannot be Spat Out, for a Neuroleptic|
|US20080226695 *||May 29, 2008||Sep 18, 2008||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20080234200 *||May 20, 2008||Sep 25, 2008||Nastech Pharmaceutical Company Inc.||Method of treatment of a metabolic disease using intranasal administration of exendin peptide|
|US20080260805 *||Apr 14, 2008||Oct 23, 2008||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20080268027 *||Jul 11, 2008||Oct 30, 2008||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20080292683 *||May 24, 2007||Nov 27, 2008||Monosolrx, Llc.||Film shreds and delivery system incorporating same|
|US20080299005 *||Oct 22, 2004||Dec 4, 2008||Meathrel William G||Disintegratable films for diagnostic devices|
|US20080318837 *||Dec 1, 2006||Dec 25, 2008||Nastech Pharmaceutical Company Inc.||Pharmaceutical Formation For Increased Epithelial Permeability of Glucose-Regulating Peptide|
|US20080318861 *||Dec 7, 2006||Dec 25, 2008||Nastech Pharmaceutical Company Inc.||Mucosal Delivery of Stabilized Formulations of Exendin|
|US20090087812 *||Oct 2, 2007||Apr 2, 2009||Ultradent Products, Inc.||Self-customizable dental treatment trays|
|US20090095313 *||May 16, 2008||Apr 16, 2009||Fuisz Richard C||Smokeless Tobacco Product, Smokeless Tobacco Product in the Form of a Sheet, Extrudable Tobacco Composition, Method for Manufacturing a Smokeless Tobacco Product, Method for Delivering Super Bioavailable Nicotine Contained in Tobacco to a User, and Packaged Smokeless Tobacco Product Sheet|
|US20090098192 *||Oct 10, 2008||Apr 16, 2009||Fuisz Richard C||Extrudable and Extruded Compositions for Delivery of Bioactive Agents, Method of Making Same and Method of Using Same|
|US20090130058 *||Nov 17, 2006||May 21, 2009||Hall Mark J||Biologically active composition comprising ethylcellulose|
|US20090136555 *||Mar 22, 2007||May 28, 2009||Crowley Michael M||Process for the preparation of a hot-melt extruded laminate|
|US20090264385 *||Mar 22, 2007||Oct 22, 2009||Crowley Michael M||Stabilized compositions containing alkaline labile drugs|
|US20100028829 *||Jul 31, 2008||Feb 4, 2010||Ultradent Products, Inc.||Chemically activated dental bleaching trays|
|US20100040727 *||Aug 18, 2008||Feb 18, 2010||Monosol Rx, Llc||Method for Improving Uniformity of Content in Edible Film Manufacturing|
|US20100150987 *||Dec 15, 2008||Jun 17, 2010||Monosol Rx, Llc||Method for Manufacturing Edible Film|
|US20100221309 *||May 13, 2010||Sep 2, 2010||Monosol Rx, Llc||Film compositions for delivery of actives|
|US20100285130 *||Apr 30, 2010||Nov 11, 2010||Monosol Rx, Llc||Coating of complexed actives in film formulations|
|US20100297232 *||May 19, 2009||Nov 25, 2010||Monosol Rx, Llc||Ondansetron film compositions|
|US20110009834 *||Feb 27, 2009||Jan 13, 2011||Lts Lohmann Therapie-Systeme Ag||Gingival wafer|
|US20110086329 *||Dec 21, 2010||Apr 14, 2011||Ranir/Dcp Corporation||Device and method for delivering an oral care agent|
|US20110142942 *||Dec 10, 2010||Jun 16, 2011||Monosol Rx, Llc||USE OF pH SENSITIVE COMPOUNDS IN TASTE MASKING OF DRUG SUBSTANCES WITHIN ORAL THIN FILM STRIPS|
|US20110160264 *||Dec 27, 2010||Jun 30, 2011||Monosol Rx, Llc||Orally administrable film dosage forms containing ondansetron|
|US20110178048 *||May 8, 2007||Jul 21, 2011||Repka Michael A||Stabilized formulation of triamcinolone acetonide|
|US20110182969 *||Mar 21, 2011||Jul 28, 2011||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20110200715 *||Apr 28, 2011||Aug 18, 2011||Monosol Rx, Llc||Multi-layer films having uniform content|
|CN101489756B||Mar 22, 2007||Aug 7, 2013||奥克思利尤姆国际控股公司||Process for the preparation of a hot-melt extruded laminate|
|EP0598606A1 *||Nov 17, 1993||May 25, 1994||JOHNSON & JOHNSON CONSUMER PRODUCTS, INC.||Extrudable compositions for topical or transdermal drug delivery|
|EP1659976A2 *||May 7, 2004||May 31, 2006||Ultradent Products, Inc.||Compositons and devices having a tray-like configuration for delivering an oral medicament and methods of manufacturing and using such compositions and devices|
|EP1659976A4 *||May 7, 2004||Mar 4, 2009||Ultradent Products Inc||Compositons and devices having a tray-like configuration for delivering an oral medicament and methods of manufacturing and using such compositions and devices|
|EP2010156A2 *||Mar 22, 2007||Jan 7, 2009||Auxilium International Holdings, Inc.||Stabilized compositions containing alkaline labile drugs|
|EP2010156A4 *||Mar 22, 2007||Jul 18, 2012||Auxilium Int Holdings Inc||Stabilized compositions containing alkaline labile drugs|
|EP3141248A1 *||Mar 22, 2007||Mar 15, 2017||Auxilium International Holdings, Inc.||Stabilized compositions containing alkaline labile drugs|
|WO1992007640A1 *||Sep 23, 1991||May 14, 1992||Fmc Corporation||Polysaccharide-based porous sheets|
|WO2007112285A2||Mar 22, 2007||Oct 4, 2007||Auxilium Pharmaceuticals, Inc.||Process for the preparation of a hot-melt extruded laminate|
|WO2007112285A3 *||Mar 22, 2007||Oct 2, 2008||Auxilium Pharmaceuticals Inc||Process for the preparation of a hot-melt extruded laminate|
|WO2011081625A1||Dec 30, 2009||Jul 7, 2011||Novartis Ag||Melt extruded thin strips containing coated pharmaceutical actives|
|WO2011081628A1||Dec 30, 2009||Jul 7, 2011||Novartis Ag||Melt extruded nicotine thin strips|
|WO2017093941A1||Dec 1, 2016||Jun 8, 2017||Niconovum Usa, Inc.||Multi-phase delivery compositions and products incorporating such compositions|
|U.S. Classification||424/676, 424/449, 424/435|
|Jun 3, 1991||FPAY||Fee payment|
Year of fee payment: 4
|May 25, 1995||FPAY||Fee payment|
Year of fee payment: 8
|May 3, 1999||FPAY||Fee payment|
Year of fee payment: 12