Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS3087860 A
Publication typeGrant
Publication dateApr 30, 1963
Filing dateDec 19, 1958
Priority dateDec 19, 1958
Publication numberUS 3087860 A, US 3087860A, US-A-3087860, US3087860 A, US3087860A
InventorsEndicott Clarence J
Original AssigneeAbbott Lab
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Method of prolonging release of drug from a precompressed solid carrier
US 3087860 A
Images(4)
Previous page
Next page
Description  (OCR text may contain errors)

United States Patent 07'' 3,087,860 METHOD OF PROLONGING RELEASE OF DRUG FROM A PRECOMPRESSED SOLID CARRIER Clarence J. Endicott, Winthrop Harbor, Ill., assignor to Abbott Laboratories, North Chicago, 111., a corporation of Illinois No Drawing. Filed Dec. 19, 1958, Ser. No. 781,433 11 Claims. (Cl. 167-82) This invention relates to a novel method of prolonging the release of a drug from a solid carrier. More particularly, the invention relates to the vapor treatment of a drug composition dispersed in a plastic carrier. This treatment fuses the individual particles of plastic into a continuous network of plastic which impedes the release of the drug from the carrier when such a composition is administered orally.

It has always been recognized in the medical art that the administration of drugs by the oral route is to be preferred and in recent years more and more emphasis has been placed on the oral administration of drugs. There are reasons why many drugs cannot be administered satisfactorily in their simplest form. For example, the drug may be too readily absorbed with the consequent danger from toxic dosage. Secondly, it may be too readily excreted and pass out of the body before the therapeutic effect can be realized or the drug may be effective but prolongation of its effect is desired to avoid multiple dosages.

Numerous attempts have been made to provide a dosage form which will solve the foregoing problems but up to the present time none of these has proven entirely satisfactory. For example, enteric coatings have been applied for many years to a wide variety of drugs in an attempt to protect the drug from gastric secretions, or to protect the stomach from the harsh effect of the drug. Enteric coatings have employed many kinds of materials and all are designed to be resistant to gastric secretions, but must be readily disintegrated in the intestinal tract in order for the drug to become effective. In every instance the enteric coating is designed to prevent release of drug in the stomach and to be destroyed or broken up in the intestinal tract. Enteric cOatings as a class depend upon some type of chemical action or reaction for their disintegration.

Another class of protective coating for medieaments is the type known as time-disintegration coatings. In these coatings a class of materials is used which is dissolved or distinguished slowly as the tablet passes through the stomach and intestine, and an amount of coating is used which is designed to allow release of the drug after a certain period of time in the body. Due to the tremendous differences in the operation of the gastrointestinal mechanism in different persons the time-disintegration coating does not work the same way in every person but rather is designed to give results based on averages.

A variation of the time-disintegration dosage form just described is one in which particles of a medicament are coated with a varying number of layers of a material which will be slowly washed away or destroyed by the gastro-intestinal fluids. In such a dosage form a portion of the drug has little or no coating for initial response, thin coatings are used for a quick follow-up response and thicker coatings are used for a delayed response.

Time-disintegration coatings as a class depend for their disintegration upon the effects of agents found in the gastro-intest-inal fluids. The enzymes, fat-solubilizers and emulsifiersin these fluids hasten the breaking-up or wearing-away of the coatings.

It is a principal object of the present invention to pro- 3,087,860 Patented Apr. 30, 1963 vide a method for the preparation of an orally effective dosage form in which the drug will be slowly released in the body.

Another object of the invention is to provide a method for the vapor treatment of a drug composition dispersed in a plastic carrier which will coalesce the individual particles of plastic to impede the release of the drug when such a composition is orally administered.

A further object of the invention is to provide a method for the preparation of an oral dosage form from which the drug will be slowly released by a substantially physical process of dissolving drug out of a solid, inert body independently of the digestive process.

Other objects and many of the inherent advantages of the present invention will become more apparent throughout the following specification and appended claims.

In the accomplishment of the foregoing objects and in accordance with the practice of this invention there is now provided a method for the vapor treatment of a combination of a drug and, if desired, a water-soluble excipient dispersed uniformly in a body of a non-toxic synthetic plastic material. Such treatment produces a continuous network within the carrier and makes it less susceptible to disintegration when such a drug combination is orally ingested. In general, the method consists of exposing a compressed mixture (conveniently in table form) of drug and plastic to the vapors of a volatile organic solvent for the plastic in a confined space for a period of time suflicient to result in softening of the surface of said plastic.

Suitable solvents include methylene chloride, ethyl acetate, ethylene dichloride and toluene. In a preferred method of operation, acetone is employed as the solvent. The compressed mixture of drug and plastic is exposed in a confined space at room temperature and atmospheric pressure for a period of from 3 to 24 hours. Alternatively, the vapor treatment may be carried out at temperatures of about 100 F. at atmospheric pressure or at considerably higher temperatures and under vacuum.

Upon drying the treated tablet, the plastic particles adhere to one another more firmly forming a porous body having a network of continuous interstices throughout the tablet. The plastic body resists disintegration during exposure to water. Before solvent vapor treatment, the

, plastic particles are so loosely held together that the tablets disintegrate within a very short time. Thus, it is believed that the treatment results in a partial solubilization of the individual particles of plastic by the solvent vapor and a fusion of one particle of plastic to another. When such a composition comes into contact with an aqueous liquid the drug is leached or diffused out of the plastic body. The amount of drug released in the early stages of the leaching process is sufficient to provide the desired initial pharmacologic response and the amount of drug released thereafter will sustain the pharmacologic response over an extended period of time. Because the releasing action is entirely physical, rather than chemical, the results are readily predictable.

The term drug is used herein in its broadest sense as indicating any substance or composition which will give a pharmacologic response. When it is said that the drug is water soluble it is meant to indicate that the drug must be soluble in aqueous liquids to at least a certain small extent but drugs which are readily soluble in water will, of course, make up the preferred group. Methamphetamine salts, hexocyclium methylsulfate, paraamino benzoic acid, ephedrine, mannitol hexanitrate, amphetamine, erythromycin salts, penicillin salts, pentobarbital, phenobarbital, atropine, belladonna, theophylline, sex hormones, hydantoins, trimethadione, watersoluble vitamins such as B and C, benzazoline, toluidine blue and related drugs are representative of the broad class of drugs which may be incorporated in compositions suitable for treatment by this new method.

The plastics to which this invention pertains may be any synthetic resinous of polymeric material which is substantially inert to gastro-intestinal liquids and which, of course, is essentially non-toxic and can be ingested without danger. The plastic mass or body may be referred to as an orally ingestible plastic carrier, in which the drug is dispersed. It is desirable that the drug be uniformly dispersed throughout the body or mass of the carrier in order that uniformity of results may be obtained. In a preferred form of the invention, it is desirable to use a plastic carrier which is not only substantially water insoluble but which will be excreted substantially unchanged except for the loss of the drug therefrom.

The polymers suitable for use in this invention must be resistant to flow, sintering or blocking at temperatures likely to be encountered in storage. While rubbery materials can be used, the manufacture of the finished product is easier if the polymer is hard, i.e., in a glassy or crystalline state at ambient temperature. Since the temperature at Which pharmaceutical products may be stored may rise as high as 105 F., the glass point of a suitable polymer should preferably be not much lower than 105 F. The glass point is defined in Flory, Principles of Polymer Chemistry, p. 56, Cornell University Press, 1953. Briefly, it is the midpoint of the narrow temperature region above which an amorphous polymer exists in a viscous or rubbery condition and below which it is hard and relatively brittle.

There are numerous polymers and copolymers which can be used successfully in this invention as will be evident to those skilled in the art. A few examples are polyethylene, polymethylmethacrylate, copolymers of methylmethacrylate and alkyl acrylates, polyvinylacetate, polyhexamethylene adipamide and the like.

The polymers can be prepared by bulk, solution, suspension, or emulsion polymerization. If the last method is used, the polymer may be coagulated into solid particles which can be readily mixed with a drug or a drug may be admixed before coagulation as will be more fully discussed hereinafter.

In the polymerization procedure, it is desirable in some cases to use a step or steps in which impurities, if present, are removed. There should be removed inhibitor, if used, residual monomer or monomers, and any remaining polymerization initiator. Methods for accomplishing these ends are known in the art. They include distillation in its various aspects such as distillation with steam or under low pressure, washing and extraction.

The composition employed in the method of this invention may be described as having discrete particles of a drug dispersed in a matrix of a plastic carrier. This composition is to be distinguished from a plastic tablet coating in which the coating completely surrounds the drug and prevents access of liquids to the drug until the coating is disrupted or destroyed. In the present instance, the plastic takes the form of a foraminous body with drug contained in the pockets or voids, but the drug is accessible to liquids and may be removed from the plastic body by a leaching or washing action without materially affecting the phyiscal condition of the plastic body.

One may add sodium chloride or other water-soluble, component or ingredient to increase the water permeability of the composition. Other water-soluble excipients or adjuvants which may be employed include dextrose, acacia, sucrose, polyethylene glycols, sorbitol, urea, polyvinylpyrrolidone, inositol, lactose, mannitol, methocel, calcium chloride, pectin and the like.

The composition employed in the method of this invention can be made in a number of ways which will be apparent to one skilled in the plastics art. One suitable way of making the composition is to thoroughly blend a plastic in powder or granular form with the drug in crystalline or granular form and then subject the mixture to heat and pressure so that the composition is converted into a solid body or mass having the drug dispersed therein. It is possible by the use of selected proportions of particles having different sizes to arrive at any desired rate of diffusion or leaching. This is an important and highly desirable feature since it enables the compounder to adjust the rate of release of the drug to a given set of conditions.

Another method is to disperse the drug in a liquid monomer, and polymerize the mass, thereby achieving an excellent dispersion of the drug in the plastic, which may then be comminuted to desired size. This method may be varied by using mixtures of monomers, and by adding polyfunctional monomers, which result in a cross-linked plastic, insolu-be in most solvents. By means of this latter technique, normally water-soluble polymers and very hydrophilic polymers, such as polyacrylic acid, may be employed in the invention.

Still other methods are contemplated. In addition to incorporation of the drug by milling or by mixing and extruding the drug-plastic combination, a drug of limited water solubility may be finely ground and suspended in a latex or aqueous dispersion of an appropriate plastic. The latex may then be coagulated by known procedures to give a finely divided crumb in which the plastic and drug are intimately associated. Alternatively, a dispersion or solution of a drug in such a latex may be spray dried or drum dried and the solid product ground and screened to give a suitable product. In another method the plastic is dissolved in a solvent solution, the drug is dispersed or dissolved therein and the suspension or solution cast as a film by known techniques. The film can be ground and screened to proper size.

The amount of drug which is suspended or dispersed in the plastic mass may be varied at will from a small but significant amount capable of giving a pharmacologic response up to the saturation point beyond which the composition will no longer have its characteristic properties as a plastic mass. In one instance it was found that up to by weight of drug based on the total weight of the composition can be employed. It will be apparent that the concentration of the drug, the particle size of the composition and the water permeability of the plastic mass provide a great deal of control over the response of the drug and may be interrelated in such a way as to give the compounder great leeway in the preparation of tailored compositions.

The composition employed in the vapor treatment method of this invention may be prepared by grinding or otherwise comminuting the plastic mass having the drug embedded therein to a desired particle size or range of particle sizes and mixing, combining or incorporating in a pharmaceutical carrier. Particle size in an important aspect of the invention since the rate of diffusion or leaching out of the drug from a given plastic after vapor treatment will be slower from a small particle than from a large particle. The particles may be recombined with tableting adjuvants in the form of conventional pharmaceutical tablets.

The following examples illustrate the invention but are not to be construed as a limitation thereof.

Example I Mg. Sodium p-aminobenzoate 8.26 Sodium chloride 24.80

Methylacrylate-methylmethacrylate copolymer 48.6

These tablets were exposed to acetone vapor in a closed container for 24 hours at room temperature and after drying were tested for release of the drug by exposure to water with the following results:

6 v r ing the tablets with water. The results are tabulated below.

P t 1 Percent Percent 5 Time of exposure in minutes f fi hg ti s true of exposure in minutes release of release of tr atment;

dtrngtbeforte grug after; 1'82, D1611 rea men a 15 29 12 22 ii 56 23 120 47 73 36 240 69 2% 480 82 90 81 Before the acetone vapor treatment, these tablets release as much as 80% of the drug in one hour or less 1S dapparent from i abgve l zl thefidmg Is 15 when exposed to water. In addition, the tablets disintei fi if g i 2 o g i er Z grate rapidly before treatment but remain intact after one t e P as w par 16 m w 6 treatment even when all the drug is leached from the the drug 1s uniformly dispersed form a continuous net- 1 p astic carrier. work of VOld spaces throughout the tablets wh1ch resist Example 1V dismtegration and permit the drug to be leached gradu- 20 ally from the plastic body. The plastic body is com- In another p r compressed tablets were p pletely intact as a single entity at the end of the leaching pared 111 a manner Wherem the amouhls of process each component are given below on a per tablet basis:

Example II Compressed tablets wherein all ingredients and amounts Methamphetamine hydrochloride 5 are on a per tablet basis were prepared in the normal Polyvmylpyrrohdone 26-41 manner; Methylacrylate-methylmethacrylate copolymer 77.37 M Talc t 5.36 Hexocyclium methylsulfate 7 5 Magnesium stearate Mithylaerylale'methylmethael'ylale P Y 30 These tablets were treated with acetone vapors in a vace uum chamber for 5 hours at a temperature of 30 C. Magnesium stearate 3-3 and a pressure of 240 mm. of mercury. The tablets were The tablets were exposed to acetone vapor in a closed then alr-dried overnight and finally oven-dried at 140 F. container for 24 hours at room tempera/[ma The dried for 48 hours to remove all traces of acetone. The treated tablets were then tested for the release of the drug by exggg g ggig gggg g; g: lg f ig 2$ 2g:

osure to water th h f ll sults: P W t e o owmg re plastic carrier remained mtact after all the drug had been removed. Before the vapor treatment, the compressed I Percent Percent tablets disintegrated rapidly in water and released the drug Tune of exposure in minutes dgellgatsgfgie toef 40 within 30 to 60 minutes treatment treatment In still other experiments, it was found that satisfactory results could be obtained so far as the gradual release of 23 i the drug and resistance to disintegration of the plastic 32 carrier were concerned when the vapor treatment of com- 6 5 pressed tablets containing other drugs and plastics here- 22 87 inbefore enumerated was carried out with volatile organic solvents such as methylene chloride, ethyl acetate and ethylene dichloride. Although acetone is the solvent of The abeve data clearly Illustrates the effect of afietohe choice, it will be apparent to those skilled in the art that treatment 011 the release of the drug from the Plashe any solvent or mixture of solvents can be used in the presrier. With an untr at ta p i lly all Of the drug ent method provided it is volatile at reasonable operating is released within 30 minutes. fter actone tre conditions and is a solvent for the particular plastic ema good initial release of the drug occurs which gives the l d as h carrier for th d dosage level necessary for the desired therapeutic effect. I l i After this initial dose, the liberation of the drug slows 1 Th h d f prolonging h release f a d f down to a more uniform pace over the next several hours. a compressed mixture f drug and an inert water l Here g the Plashe Phh afiihere t0 eaehpther more ble, non-toxic, non-brittle, synthetic polymer having a tenacwusly to prevent dlsmtegratwn and provlde gradual glass point of at least 105 P. which comprises exposing release of the drug. said mixture to the vapors of a 'volatile organic solvent for Exam le 1 0 said polymer in a confined space for a period of time sufp ficient to result softening the surface of said polymer The following for-mualtion was compressed into tablets and thus fuse The lhdlvldual P y Pameles throughout wherein all ingredients and amounts are given on a p the mixture into a foraminous structure to further embed tablet basis: the drug thereinlMg 2. The product produced by the method of claim 1. Hexocyclium th l lfate 100 3. A method as claimed in claim 1 wherein the polymer Carbowax 0 117 is a co-polymer of methylacrylate and methylmethacrylate. Methylacrylateqnethylmethacrylate 1 117 4. A method as claimed in claim 3 wherein the solvent Talc 13,3 employed is selected from the group consisting of acetone, Magnesium stearate 6,6 methylene chloride, ethyl acetate, ethylene dichloride and toluene. The tablets were thereafter subjected to acetone vapors 5. The method of prolonging the release of a drug in a closed container for 3 hours at a temperature of 25 from an inert, water insoluble, non-toxic, non-brittle, syn- C. The tablets were then air dried and the release of the thetic polymer carrier having a glass point of at least 105' drug from the tablets was determined in vitro by contact- F. which comprises exposing a compressed tablet of said drug and said carrier to acetone vapors in a confined space for a sufficient period of time to soften and coalesce the individual particles in said carrier into a foraminous structure throughout the tablet to further embed the drug therein.

6. The product produced by the method of claim 5.

7. A method as claimed in claim 5 wherein the drug is selected from the group consisting of hexocyclium methylsulfate, methamphetamine hydrochloride, nicotinic acid, phenobarbital sodium and sodium paraminobenzoate.

8. A method as claimed in claim 5 wherein the polymer carrier is selected from the group consisting of polyethylene, polyvinylacetate, polymethylmethacrylate and methylacrylate-methylmethacrylate co-polymers.

9. The method of prolonging the release of methamphetamine hydrochloride from a non-toxic, inert, water insoluble, non-brittle, synthetic methylacrylate-methylmethacrylate co-polymer which comprises exposing a compressed tablet of said hydrochloride and said c0- polymer to acetone vapors in a vacuum chamber for about 5 hours at a temperature of about 30 C. and a pressure of about 240 millimeters of mercury to fuse the individual particles of co-polymer throughout the tablet into a foraminous structure to further embed the drug therein.

10. A method of prolonging the release of hexocyclium methylsulfate from a non-toxic, inert, water insoluble, non-brittle, synthetic methylacrylatemethylmethacrylate co-polymer which comprises exposing a compressed tablet of said sulfate and said co-polymer to acetone vapors in a closed container for about 24 hours at room temperature to fuse the individual particles of co-polymer throughout the tablet into a foraminous structure to further embed the drug therein.

'11. The method of treating the human body which comprises administering to a human host the product produced by the method of claim 5, said product being 3 adapted to release an efiective amount of drug gradually over a period of time during which the said product is present in the body.

References Cited in the file of this patent UNITED STATES PATENTS Re. 24,090 Diamond Nov. 15, 1955 312,041 Upjohn Feb. 10, 1885 2,149,005 Bockmiihl et a1 Feb. 28, 1939 2,385,920 Jenkins Oct. 2, 1945 2,478,182 Consolazio Aug. 9, 1949 2,707,201 Fernald et al. Apr. 26, 1955 2,719,093 -Voris Sept. 27, 1955 2,806,256 Smith-Johannsen Sept. 17, 1957 2,877,159 Lachman et a1 Mar. 10, 1959 2,894,289 Harper et al. July 14, 1959 2,928,769 Gaunt Mar. 15, 1960 2,928,771 Gaunt Mar. 15, 1960 2,955,982 Moeller et al. Oct. 11, 1960 2,987,455 Levesque June 6, 1961 FOREIGN PATENTS 548,310 Canada Nov. 5, 1957 665,073 Great Britain Jan. 16, 1952 OTHER REFERENCES Kennon: Dissertation Abstracts, vol. 16, No. 10, page 1889, December 1956, publication No. 18,412, Interaction Studies of Cationic Drugs With Anionic Poly Electriolytes, 103 pages, $1.50, Mic. 56-3004, University of Wisconsin, 1956.

Dragstedt: J.A.M.A., vol. 168, No. 12, Nov. 22, 1958, pp. 1652-1655.

Doerr et al.: Tablet Coatings: Cellulose High Polymers, I.A.Ph.A. Sci. ed. 43 (7), pp. 433-436, July 1954.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US312041 *Feb 10, 1885 Process of making pills
US2149005 *Nov 3, 1936Feb 28, 1939Winthrop Chem Co IncShaped medicinal preparation
US2385920 *Dec 19, 1941Oct 2, 1945Pittsburgh Plate Glass CoPlasticization of plastics
US2478182 *Jan 16, 1945Aug 9, 1949William V ConsolazioSodium chloride tablet
US2707201 *May 5, 1951Apr 26, 1955Richardson CoPorous storage battery separator and method of making
US2719093 *Jun 3, 1952Sep 27, 1955William H VorisMethods of applying plastic coatings
US2806256 *Jun 25, 1954Sep 17, 1957S J Chemical CompanyMethod of making microporous film
US2877159 *Apr 26, 1957Mar 10, 1959Ciba Pharm Prod IncMethod for preparing tablet granulations
US2894289 *Mar 1, 1956Jul 14, 1959Dow Chemical CoMethod of making permeselective membranes
US2928769 *Jul 22, 1957Mar 15, 1960Strong Cobb And Company IncProduction of controlled release medicaments
US2928771 *May 29, 1959Mar 15, 1960Strong Cobb And Company IncProduction of orally administrable controlled release medicaments
US2955982 *Oct 22, 1957Oct 11, 1960Parmelee Pharmaceutical CompanContinuous process for internally reinforcing salt tablets
US2987455 *Aug 7, 1956Jun 6, 1961Rodney G HoffMethod and apparatus for reactor safety control
USRE24090 *Nov 15, 1955 Impregnated salt tablet
CA548310A *Nov 5, 1957Chloride Electrical Storage CoDiaphragms for use in ion exchange processes
GB665073A * Title not available
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3138544 *May 3, 1961Jun 23, 1964British Drug Houses Canada LtdMicrobial sensitivity testing device
US3198700 *May 29, 1961Aug 3, 1965Blessings IncSedative tablet and method for producing the same
US3247066 *Sep 12, 1962Apr 19, 1966Parke Davis & CoControlled release dosage form containing water-swellable beadlet
US3325365 *Apr 2, 1963Jun 13, 1967Ciba Geigy CorpEnteric composition for tablet compression coating
US3432592 *Aug 28, 1963Mar 11, 1969Ciba Geigy CorpInjection-moulded oral medicament in solid form
US3440320 *Oct 11, 1966Apr 22, 1969Mortimer D SacklerChelated suppository and method of using same
US3453360 *Apr 27, 1966Jul 1, 1969Abbott LabUniversally useful stock material for manufacturing plastic dosage units by compression tableting processes
US3927206 *Jul 12, 1974Dec 16, 1975Hydrophilics Int IncCopolymer containing medicaments
US3995632 *Sep 30, 1974Dec 7, 1976Alza CorporationOsmotic dispenser
US4547359 *Mar 21, 1984Oct 15, 1985Boehringer Ingelheim KgPolyacrylate material with release rate independent of size and surface area
US4595587 *Jul 3, 1985Jun 17, 1986Boehringer Ingelheim KgDivisible pharmaceutical tablet with delayed active ingredient release
US4704284 *Aug 12, 1982Nov 3, 1987Pfizer Inc.Long-acting matrix tablet formulations
US4851231 *Mar 16, 1987Jul 25, 1989Alza CorporationSystem for delivering drug in selected environment of use
US4851232 *Jun 8, 1987Jul 25, 1989Alza CorporationDrug delivery system with means for obtaining desirable in vivo release rate pattern
US4863744 *Mar 16, 1987Sep 5, 1989Alza CorporationProtective coatings
US5011694 *Aug 1, 1989Apr 30, 1991Rohm GmbhExposing matrix of compressed mixture of powdered drug and polymer to vapor of lower alcohol
US5153002 *Aug 23, 1991Oct 6, 1992University Of MontrealBiocompatible gradient controlled release implant
US5603956 *Jun 16, 1994Feb 18, 1997Labopharm Inc.Cross-linked enzymatically controlled drug release
US5616343 *Mar 25, 1993Apr 1, 1997Labopharm, Inc.Cross-linked amylose as a binder/disintegrant in tablets
US5807575 *Feb 14, 1997Sep 15, 1998Rougier Inc.Manufacture of cross-linked amylose useful as a excipient for control release of active compounds
US6607748Jun 29, 2000Aug 19, 2003Vincent LenaertsCross-linked high amylose starch for use in controlled-release pharmaceutical formulations and processes for its manufacture
US7829120Sep 11, 2006Nov 9, 2010Labopharm Inc.once a day oral administration formulation contains trazodone or salt, phosphorus oxychloride cross-linked high amylose starch, hydroxypropylmethylcellulose, sodium stearyl fumarate, colloidal silica, optional cetylpyridinium chloride and alganic acid; antidepressant; sleep disorder; sustained release
US7846477 *Oct 9, 2003Dec 7, 2010Abbott Gmbh & Co. KgMethod for producing solid galenic formulations using a crosslinked non-thermoplastic carrier
US7890171 *Apr 20, 2007Feb 15, 2011Cardiac Pacemakers, Inc.Sensors having protective eluting coating and method therefor
US7988998Apr 22, 2005Aug 2, 2011Labopharm Inc.Sustained-release tramadol formulations with 24-hour efficacy
US8131364Jan 4, 2011Mar 6, 2012Cardiac Pacemakers, Inc.Sensors having protective eluting coating and method therefor
US8298565Jul 14, 2006Oct 30, 2012Micell Technologies, Inc.Polymer coatings containing drug powder of controlled morphology
US8414919Oct 15, 2010Apr 9, 2013Angelini Labopharm, LlcSustained drug release composition
US8487002Apr 22, 2005Jul 16, 2013Paladin Labs Inc.Controlled-release compositions
US8636767Oct 2, 2007Jan 28, 2014Micell Technologies, Inc.Surgical sutures having increased strength
US8758429Sep 6, 2012Jun 24, 2014Micell Technologies, Inc.Polymer coatings containing drug powder of controlled morphology
EP0355470A2 *Jul 28, 1989Feb 28, 1990Röhm GmbhPharmaceutical form with sustained release, and process for its preparation
WO2007002238A2 *Jun 21, 2006Jan 4, 2007James DeyoungDrug/polymer composite materials and methods of making the same
Classifications
U.S. Classification424/419, 514/356, 514/567, 514/654, 514/270
International ClassificationA61K9/20, A61K9/22
Cooperative ClassificationA61K9/2095, A61K9/2027
European ClassificationA61K9/20P, A61K9/20H6B