WO1992011038A1 - Polyamine drug-resin complexes - Google Patents
Polyamine drug-resin complexes Download PDFInfo
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- WO1992011038A1 WO1992011038A1 PCT/US1991/009463 US9109463W WO9211038A1 WO 1992011038 A1 WO1992011038 A1 WO 1992011038A1 US 9109463 W US9109463 W US 9109463W WO 9211038 A1 WO9211038 A1 WO 9211038A1
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin
Definitions
- the present invention relates to oral pharmaceutical preparations which comprise a pharmacologically-active polyamine drug bound to a cation-exchange resin to provide a drug-resin complex having a drug content greater than one equivalent of amine per equivalent of cation-exchange capacity.
- the drug-resin complex is optionally coated with a water-permeable diffusion barrier coating that is insoluble in gastrointestinal fluids thereby providing a controllable release of drug under conditions encountered in the gastrointestinal tract.
- Sustained or prolonged-release dosage forms provide a controlled and constant supply of drug to an organism.
- the control of cough, sleep, enuresis, and migraine headaches are all benefits obtained from such a controlled release of a specific drug.
- controlled release of antimicrobials can be obtained through such a dosage form.
- Such a controlled release of drugs eliminates the need to interrupt sleep to take medication, and can also prevent missed doses. They also provide the convenience of daytime dosing where the dosage form can be taken first thing in the morning and provide therapeutic levels of the drug throughout the day.
- a controlled drug-release system delivers drugs in a manner that will maintain therapeutically effective plasma levels over a period of time that is significantly longer than that which is given by a typical drug dosage form.
- Uncoated ion-exchange resin-drug complexes which delay release of a drug in the gastrointestinal tract are described in U.S. Patent No. 4,788,055 and 2,990,332.
- uncoated complexes provide only a relatively short delay of drug release in comparison with the preparations of this invention and provide poor control of drug release because the control is limited to variation in particle size and cross-linkage of the sulfonic acid-type resin used to prepare the adsorption compounds.
- Various coated resin-drug complexes have been reported (e.g., in U.S. Patent Nos. 3,138,525; 3,499,960; and 3,594,470; Belgian Patent No. 729,827; German Patent No. 2,246,037; and Borodkins et al., Journal of Pharmaceutical Science. Vol. 60, pages 1523-1527, 1971), but none are believed to employ the preparations of the subject invention or to provide the controllable release obtained with the present preparations.
- the present invention provides controlled-release pharmaceutical compositions obtained by complexing greater than one equivalent of a polyamine drug with a pharmaceutically acceptable cation-exchange resin and optionally coating such complexes with a substance that will act as a barrier to control the diffusion of the drug from its core complex into the gastrointestinal fluids.
- the coated drug-resin complex When the coated drug-resin complex is suspended in an aqueous dosage form or when it contacts gastrointestinal fluids, it expands to its swollen state, and in doing so, ruptures the diffusion barrier coating. The result is loss of control of the diffusion of released drug.
- Controlled-release drugs for use in the gastrointestinal tract are described in U.S. Patent Numbers 4,847,077, and 4,221,778, and European Patent Application 254,811, all to Raghunathan; and European Patent Application 254,822, to Chow et al.
- the method described therein for preparing products having controlled release properties involved a three-step process: (i) preparation of a drug-resin complex; (ii) treating this complex with a suitable Impregnating agent; and (iii) coating the particles of treated complex with a water-permeable diffusion barrier.
- European Patent Application 249,949, to Sellassie et al. describes three-component coated complexes containing a neutral polymeric binder such as hydroxypropylcellulose.
- Coated drug-resin complexes which do not require any such impregnation, and yet which do not undergo swelling sufficient to rupture the diffusion barrier coating when placed in contact with an aqueous vehicle or with gastrointestinal fluids, are described in European Patent Application Number 367,746, to Kelleher, W.J. et al., published May 9, 1990. This document is incorporated herein in its entirety by reference.
- a certain category of drugs presents difficulties in this latter respect when used with ion-exchange resin-based controlled release systems: these are basic drugs with more than one amine functional group, i.e. polyamine drugs.
- a tenet of ion-exchange technology is that the strength of the binding is increased as the number of binding sites on a molecule is increased.
- a negative consequence of this strengthened binding is that drug molecules bound by two or more sites might be released too slowly or incompletely under conditions encountered in the gastrointestinal tract.
- An illustrative example is provided by Amsel et al., Pharmaceutical Technology.
- polyamine drug resin complexes of the instant invention overcome these delivery and taste-masking problems. Without being limited by theory, it is believed that by binding more than one equivalent of a polyamine drug to a cation-exchange resin (i.e. in a ratio of greater than one equivalent of amine per equivalent of cation-exchange capacity) it would be possible to provide drug-resin complexes which provide both an immediate release of the drug present in excess of one equivalent and a slower or sustained release of the remaining drug. In other words, each polyamine drug molecule would be bound to the resin substantially by only one of its amine groups and would therefore occupy only one binding site on the resin.
- polyamine drug-resin complexes of the instant invention when added to gastrointestinal fluids will (i) rapidly release a portion of the polyamine drug bound in excess of 1 equivlaent, (ii) release the remaining portion of drug at a slower rate so as to provide a sustaining dose, and (iii) release a total amount of drug that is substantially in excess of the total amount released from a resin complex which contains the same polyamine drug loaded at a level of one equivalent or less per equivalent of cation-exchange capacity.
- An oral pharmaceutical composition in unit dosage form comprising cation-exchange resin particles ranging from about 10 to about
- said particles having a pharmacologically-active polyamine drug bound thereto at a capacity greater than 1 equivalent of amine per equivalent of cation-exchange capacity, wherein said composition provides controlled release of said active drug.
- the term water-permeable is used to indicate that the fluids of the alimentary canal will permeate or penetrate the optional barrier coating film with or without dissolving the film or parts of the film.
- a lighter or heavier application thereof is required so that the drug does not leach out from the complex to an extent of more than 4% in artificial saliva at 20-40°C in 2 minutes.
- regularly shaped particles refer to those particles which substantially conform to geometric shapes such as spherical, elliptical, cylindrical and the like. These shapes are ordered according to established geometric principles.
- regularly shaped ion-exchange resins of this type are exemplified by Dow XYS-40010.00 (supplied by Dow Chemical Company), and to the drug-resin complexes formed by binding drugs to these resins.
- irregularly shaped particles refers to those particles excluded from the above definition, such as those particles with amorphous shapes with increased surface areas due to surface area channels or distortions.
- irregularly shaped ion-exchange resins of this type are exemplified by Amberlite IRP-69 (supplied by Rohm and Haas), and to the drug-resin complexes formed by binding drugs to these resins.
- meq is an abbreviation for milllequlvalent(s).
- drugs that are suitable for use in these preparations are basic, having at least two amino or substituted amino moieties available for binding.
- examples of drugs useful in the present invention include, but are not limited to, acetophenazine, amitriptyline, brompheniramine, carbinoxamine, chlorcyclizine, chlorpheniramine, chlorpromazine, clonidine, cyclizine, desipramine, dexbrompheniramine, dexchlorpheniramine, doxylamine, ergotamine, fluphenazine, hydroxychloroquine, hydroxyzine, imipramine, meclizine, mesoridazine, methdilazine, methysergide, pheniramine, pyrilamine, tripelennamine, triprolidine, promazine, and quinidine, and mixtures thereof.
- the ion-exchange resins suitable for use in these preparations are water-insoluble and consist of a pharmacologically inert organic or inorganic matrix containing covalently bound functional groups that are ionic or capable of being ionized under the appropriate conditions of pH.
- the organic matrix may be synthetic (e.g., polymers or copolymers of acrylic add, methacrylic acid, sulfonated styrene, sulfonated divinylbenzene), or partially synthetic (e.g., modified cellulose and dextrans).
- the inorganic matrix can also be, e.g., silica gel modified by the addition of ionic groups.
- the covalently bound ionic groups may be strongly acidic (e.g., sulfonic add) or weakly acidic (e.g., carboxylic add).
- those types of cation-exchangers suitable for use in ion-exchange chromatography and for such applications as deionization of water are suitable for use in these controlled release drug preparations.
- Such ion-exchangers are described by H.F. Walton in "Principles of Ion Exchange” (pp. 312-343) and “Techniques and Applications of Ion-Exchange Chromatography” (pp. 344-361) in Chromatography. (E. Heftmann, editor), Van Nostrand Reinhold Company, New York (1975), incorporated by reference herein.
- the cation-exchange resins useful in the present invention preferably have exchange capacities below about 6 meq/gram and more preferably below about 5.5 meq/gram.
- these cation-exchange resins contain covalently bound ionic groups which are strongly acidic.
- the size of the ion-exchange particles should preferably fall within the range of about 40 microns to about 150 microns. Particle sizes substantially below the lower limit are difficult to handle in all steps of the processing. Particle sizes substantially above the upper limit, e.g., commercially-available ion-exchange resins having a spherical shape and diameters up to about 1000 microns, are gritty in liquid dosage forms and have a greater tendency to fracture when subjected to drying-hydrating cycles.
- Representative resins useful in this invention include Amberlite IRP-69 (obtained from Rohm and Haas) and Dow XYS-40010.00 (obtained from The Dow Chemical Company). Both are sulfonated polymers composed of polystyrene cross-linked with 8% of divinylbenzene, with an ion-exchange capacity of about 4.5 to 5.5 meq/gram of dry resin (H + -form). Their essential difference is in physical form.
- Amberlite IRP-69 consists of irregularly-shaped particles with a size range of 47 microns to 149 microns, produced by milling the parent large-sized spheres of Amberlite IRP-120.
- the Dow XYS-40010.00 product consists of spherical particles with a size range of 45 microns to 150 microns.
- the binding may be performed, for example, as a batch or column process, as is known in the art.
- the drug-resin complexes are prepared by a batch process.
- the drug-resin complex thus formed is collected by filtration and washed with ethanol and/or water to insure removal of any unbound drug.
- the complexes are usually air-dried in trays at room temperature.
- the coating materials may be any of a large number of natural or synthetic film-formers used singly, in admixture with each other, and in admixture with plasticizers, pigments and other substances to alter the characteristics of the coating.
- the major components of the coating should be insoluble in, and permeable to water.
- a water-soluble substance such as methyl cellulose
- the coating materials may be applied as a suspension in an aqueous fluid or as a solution in organic solvents. Suitable examples of such coating materials are described by R.C. Rowe in Materials used in Pharmaceutical Formulation. (A.T. Florence, editor), Blackwell Scientific Publications, Oxford, 1-36 (1984), incorporated by reference herein.
- the water-permeable diffusion barrier is selected from the group consisting of ethyl cellulose, methyl cellulose, and mixtures thereof.
- coated drug-resin particles prepared according to the teachings of this invention are suitable for suspending in an essentially aqueous vehicle with the only restrictions on its composition being (i) an absence of, or very low levels of ionic ingredients, and (ii) a limitation on the concentrations of water-miscible organic solvents, such as alcohol, to those levels which do not cause dissolution of the diffusion barrier coating.
- These coated drug-resin particles are also suitable for placing into capsules as a solid dosage form.
- Moisture determinations were performed with a Mettler LP16 infrared heater on a PE160 balance. Because of the variation in moisture content over relatively short time periods, moisture determinations were always performed immediately prior to the use of any resin or drug-resin complex, and corrections were made in quantities taken so that all values are expressed on a dry weight basis.
- Determinations of release of drug from drug-resin complexes were performed with equipment that conforms to the USP Dissolution Apparatus 2. In all instances, a two-bladed paddle rotating at 50 rpm was used.
- the release medium was either 900 mL of 0.1 N HCl or 0.1 N HCl converted in situ to 0.07 M sodium phosphate buffer (pH 7.2), by adding 24.8 g of trisodium phosphate dodecahydrate to 900 mL of 0.1 N HCl. Release media were maintained at 37°C.
- Sufficient drug-resin complexes were added to provide the following doses (expressed as the commonly administered forms): doxylamine succinate, 15 mg; chlorpheniramine maleate, 16 mg; and pheniramine maleate, 25 mg.
- the drug-resin complexes were added to the release media as dry powders. At appropriate time Intervals, samples of approximately 10 mL were removed from the dissolution beaker and immediately filtered through a syringe-mounted filter. Exactly 5.0 mL of the filtrate was reserved for analysis. The remainder of the filtrate was returned to the dissolution beaker. Particles of drug-resin complex adhering to the filter were rinsed into the dissolution beaker with exactly 5.0 mL of fresh release medium.
- the absorbances of the filtered samples were measured at the wavelength of the peak in the ultraviolet spectrum with a Perkin-Elmer model 552 or Lambda 3B UV/VIS spectrophotometer. The absorbance values were converted to percentages of added drug that were released.
- the samples were analyzed by HPLC on a reverse phase phenyl column using methanol:water:acetic add (60:40:2 by volume, with 5 mM sodium hexane sulfonate) with a Waters model 6000A pump and a model 450 variable wavelength detector set at the wavelength of peak absorption for the drug. Peak areas were converted to percentage of drug released. Diffusion barrier coatings were applied with a Glatt CPCG-5 Wurster-type fluid-bed coater.
- the level of coating contained on the coated drug-resin complex was determined by stripping the coating with an appropriate solvent, evaporating the solvent, and weighing the dried residue. An accurately weighed sample of coated drug-resin complex of about 2.0 g was placed in a 30-mL glass centrifuge tube. Twenty mL of ethanol was added and the mixture was stirred occasionally over a period of about 30 minutes. The mixture was centrifuged and the supernatant was decanted into a round bottom flask. The extraction, centrifugation and decanting were repeated three more times. The combined ethanolic extracts were concentrated to dryness in a rotary vacuum evaporator.
- the flask containing the dried residue was rinsed four times, each with several mL of methylene chloride/acetone (9:1 v/v).
- the rinsings were transferred to a tared aluminum pan and allowed to evaporate in a hood.
- the pan was heated at 55°C for 30 minutes, allowed to cool, and weighed.
- the increase over the tare weight was attributed to the ethylcellulose coating.
- the values obtained agreed very well with the amount of coating applied in the fluid-bed coater.
- This example illustrates a drug-resin complex comprising doxylamine bound to an Amberlite IRP-69 resin.
- This drug-resin complex contains 1.92 equivalents of doxylamine per equivalent of cation-exchange capacity.
- the release profile for this drug-resin complex in simulated gastric fluid is compared to that for a doxylamine complex containing less than 1 equivalent of drug per equivalent of cation-exchange capacity.
- the resin is added to a round bottom flask, which is fitted with a condenser, and which contains 50 mL of water, pre-warmed to
- the doxylamine (free base) is added and the mixture is held at 100°C with mixing for 2 hours.
- the mixture is suction filtered and the retained drug-resin cake is washed with ethanol until the washings have a negligible absorbance at 261 nm.
- the drug-resin complex which has now been washed free of unbound drug, is dried at room temperature. Analysis shows that the complex contains 57.0% by weight of doxylamine.
- the resin is added to a round bottom flask containing 20 mL of water, pre-warmed to 60°C.
- the doxylamine succinate is added and the mixture is held at 60°C with mixing for 2 hours.
- the mixture is suction filtered and the retained drug-resin cake is washed with water until the washings have a negligible absorbance at 261 nm.
- the drug-resin complex which has now been washed free of unbound drug, is dried at room temperature. Analysis shows that the complex contains 40.2% by weight of doxylamine.
- This example illustrates a drug-resin complex comprising pheniramine bound to an Amberlite IRP-69 resin.
- This drug-resin complex contains 1.93 equivalents of pheniramine per equivalent of cation-exchange capacity.
- the release profile for this drug-resin complex in simulated gastric fluid is compared to that for a pheniramine complex containing less than 1 equivalent of drug per equivalent of cation-exchange capacity.
- the resin is added to a round bottom flask, which is fitted with a condenser, and which contains 25 mL of water, pre-warmed to
- the pheniramine (free base) is added and the mixture is held at 100°C with mixing for 3 hours.
- the mixture is suction filtered and the retained drug-resin cake is washed with ethanol until the washings have a negligible absorbance at 260 nm.
- the drug-resin complex which has now been washed free of unbound drug, is dried at room temperature. Analysis shows that the complex contains 54.2% by weight of pheniramine.
- the resin is added to a round bottom flask containing 10 mL of water, pre-warmed to 60°C.
- the pheniramine maleate is added and the mixture is held at 60°C with mixing for 3 hours.
- the mixture is suction filtered and the retained drug-resin cake is washed with water until the washings have a negligible absorbance at 260 nm.
- the drug-resin complex which has now been washed free of unbound drug, is dried at room temperature. Analysis shows that the complex contains 35.9% by weight of pheniramine. (C).
- the complexes from (A) and (B) of this example are found to give the following release profiles for pheniramine when placed in 0.1 N HCl (simulated gastric fluid). The release of pheniramine from complex (A) is substantially greater than from complex (B).
- This example illustrates a drug-resin complex comprising chlorpheniramine bound to an Amberlite IRP-69 resin and the effect of subsequently coating the resin with a diffusion barrier coating.
- These drug-resin complexes (both uncoated and coated) contain 1.72 equivalents of chlorpheniramine per equivalent of cation-exchange capacity.
- the release profiles for these drug-resin complexes in simulated gastric fluid are compared to those for chlorpheniramine complexes (both uncoated and coated) containing less than 1 equivalent of drug per equivalent of cation-exchange capacity.
- the drug-resin cake retained on the filter is washed with 5 L of ethanol.
- the washed drug-resin cake is slurried with 3 L of ethanol, and the slurry is suction filtered.
- the drug-resin cake retained on the filter is washed with 4.5 L of ethanol.
- the final washing is found to have a negligible absorbance at 264 nm.
- the washed drug-resin cake is spread out to dry at room temperature. Analysis shows that the complex contains 54.7% by weight of chlorpheniramine.
- Ethyl Acetate 1900 g The ethyl cellulose is dissolved in the ethyl acetate with stirring.
- the resin complex is placed in a pre-warmed fluid-bed coating apparatus and fluidized with 70°C intake air.
- the coating solution is applied at a rate of 20-25 g/minute until 2000 g has been applied. Fluidization is continued with the heated air for 2 minutes after the termination of the application of the coating solution.
- the resin is added to a 70 L round bottom flask containing 15 L of water pre-warmed to 60°C.
- the chlorpheniramine maleate is added and the mixture is stirred for one hour at 60°C.
- the contents of the flask are transferred to a 20 L polyethylene bucket and allowed to stand at room temperature until most of the complex has settled.
- the supernatant liquid containing suspended fine particles is decanted and discarded.
- the sedimented complex is slurried with 3.0 L of water, and the slurry is suction filtered.
- the drug-resin cake retained on the filter is washed with water (3 ⁇ 1 L).
- the washed drug-resin cake is further washed with 5 L of ethanol.
- the final washing is found to have a negligible absorbance at 264 nm.
- the washed drug-resin cake is spread out to dry at room temperature. Analysis shows that the complex contains 39.2% by weight of chlorpheniramine.
- the ethyl cellulose is dissolved in the ethyl acetate with stirring.
- the resin complex is placed in a pre-warmed fluid-bed coating apparatus and fluidized with 70°C intake air.
- the coating solution is applied at a rate of 20-25 g/minute until 2000 g has been applied. Fluidization is continued with the heated air for 2 minutes after the termination of the application of the coating solution.
- the complexes from (A), (B), (C), and (D) of this example are found to give the following release profiles for chlorpheniramine when placed in 0.1 N HCl (simulated gastric fluid).
- the release of chlorpheniramine from uncoated complex (A) is substantially greater than from uncoated complex (C).
- the uncoated complex from (A) can be successfully coated with a diffusion barrier coating to provide a sustained release of drug as exemplified by the coated complex from (B).
- This example illustrates the preparation of a chlorpheniramine-Dow XYS Resin complex and the determination of its sequential release of chlorpheniramine into simulated gastric fluid and pH 7.2 buffer.
- the chlorpheniramine (free base) is added and the mixture is held at 100°C with mixing for 2 hours.
- the mixture is suction filtered and the retained drug-resin cake is washed with ethanol until the washings have a negligible absorbance at 264 nm.
- the drug-resin complex which has now been washed free of unbound drug, is dried at room temperature. Analysis shows that the complex contains 53.0% by weight of chlorpheniramine.
- the complex from (A) is found to give the following release profile for chlorpheniramine.
- the release is determined in 0.1 N HCl (simulated gastric fluid) for 60 minutes and then in pH 7.2 phosphate buffer for an additional 60 minutes.
- the release of chlorpheniramine into the simulated gastric fluid during the first 60 minutes is similar to the release observed for the drug resin complexes described in Examples I (A), II (A), and III (A).
- the change to the pH 7.2 buffer gives a total release of the remaining bound chlorpheniramine.
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Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR919107173A BR9107173A (pt) | 1990-12-21 | 1991-12-16 | Complexos de medicamentos de poliamina e resina |
JP4503722A JPH06504059A (ja) | 1990-12-21 | 1991-12-16 | ポリアミン薬物−樹脂複合体 |
SK594-93A SK59493A3 (en) | 1990-12-21 | 1991-12-16 | Polyamine drug-resin complexes |
CS931197A CZ119793A3 (en) | 1990-12-21 | 1991-12-16 | Pharmaceutical preparation |
AU91687/91A AU663695B2 (en) | 1990-12-21 | 1991-12-16 | Polyamine drug-resin complexes |
NO93932212A NO932212L (no) | 1990-12-21 | 1993-06-16 | Polyaminmedikament-harpikskomplekser |
FI932842A FI932842A (fi) | 1990-12-21 | 1993-06-18 | Polyamina laekemedelshartskomplex |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US63229090A | 1990-12-21 | 1990-12-21 | |
US632,290 | 1990-12-21 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992011038A1 true WO1992011038A1 (en) | 1992-07-09 |
Family
ID=24534913
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1991/009463 WO1992011038A1 (en) | 1990-12-21 | 1991-12-16 | Polyamine drug-resin complexes |
Country Status (17)
Country | Link |
---|---|
EP (1) | EP0563294A1 (pt) |
JP (1) | JPH06504059A (pt) |
CN (1) | CN1063221A (pt) |
AU (1) | AU663695B2 (pt) |
BR (1) | BR9107173A (pt) |
CA (1) | CA2098200A1 (pt) |
CZ (1) | CZ119793A3 (pt) |
FI (1) | FI932842A (pt) |
HU (1) | HUT74642A (pt) |
IE (1) | IE914513A1 (pt) |
MX (1) | MX9102753A (pt) |
MY (1) | MY107811A (pt) |
NO (1) | NO932212L (pt) |
NZ (1) | NZ241097A (pt) |
PT (1) | PT99912A (pt) |
SK (1) | SK59493A3 (pt) |
WO (1) | WO1992011038A1 (pt) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
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ES2097087A1 (es) * | 1994-08-01 | 1997-03-16 | Univ Sevilla | Sistema de liberacion controlada de morfina y otros farmacos solubles en agua por complejacion con sustancias polimericas. |
US5731005A (en) * | 1993-08-13 | 1998-03-24 | Vitaphore Corporation | Hydrogel-based microsphere drug delivery systems |
US5932248A (en) * | 1993-11-18 | 1999-08-03 | Paragon Medical Limited | Controlled release preparations for cytotoxic or cytostatic drugs |
US6001392A (en) * | 1996-12-20 | 1999-12-14 | Warner-Lambert Company | Antitussive drugs delivered by ion exchange resins |
KR20020016069A (ko) * | 2000-08-24 | 2002-03-04 | 민경윤 | 마크로라이드계 항생제의 경구투여용 조성물 및 이의 제조방법 |
WO2005023217A2 (en) * | 2003-09-03 | 2005-03-17 | Mallinckrodt Inc. | Granular sustained release preparation and production thereof |
CZ301557B6 (cs) * | 1998-07-17 | 2010-04-14 | Bristol-Myers Squibb Company | Entericky povlecená farmaceutická tableta a zpusob její prípravy |
EP2500016A1 (en) | 2011-03-18 | 2012-09-19 | Laboratorios Del. Dr. Esteve, S.A. | Doxylamine resinate complex |
WO2015076821A1 (en) * | 2013-11-22 | 2015-05-28 | Tris Pharma, Inc. | Novel clonidine formulation |
US11918689B1 (en) | 2020-07-28 | 2024-03-05 | Tris Pharma Inc | Liquid clonidine extended release composition |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN100415297C (zh) * | 2006-08-28 | 2008-09-03 | 浙江大学 | 基于阳离子交换树脂的锌补充剂的制备方法 |
CN100411629C (zh) * | 2006-08-28 | 2008-08-20 | 浙江大学 | 一种缓释型补铁剂的制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4221778A (en) * | 1979-01-08 | 1980-09-09 | Pennwalt Corporation | Prolonged release pharmaceutical preparations |
EP0171528A2 (en) * | 1984-07-18 | 1986-02-19 | Pennwalt Corporation | Controlled release pharmaceutical preparations |
EP0294103A1 (en) * | 1987-06-02 | 1988-12-07 | Takeda Chemical Industries, Ltd. | A sustained-release preparation and production thereof |
EP0367746A2 (en) * | 1988-11-02 | 1990-05-09 | Richardson-Vicks, Inc. | Sustained release drug-resin complexes |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL90245A (en) * | 1988-05-11 | 1994-04-12 | Glaxo Group Ltd | Resin adsorption containing ranitidine together with synthetic resin replaces cations, its preparation and pharmaceutical preparations containing it |
FR2634377B1 (fr) * | 1988-06-30 | 1991-09-27 | Cortial | Nouvelle forme pharmaceutique a liberation prolongee a base d'un complexe resine-principe actif |
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1991
- 1991-12-16 HU HU9301819A patent/HUT74642A/hu unknown
- 1991-12-16 AU AU91687/91A patent/AU663695B2/en not_active Ceased
- 1991-12-16 BR BR919107173A patent/BR9107173A/pt not_active Application Discontinuation
- 1991-12-16 CZ CS931197A patent/CZ119793A3/cs unknown
- 1991-12-16 SK SK594-93A patent/SK59493A3/sk unknown
- 1991-12-16 CA CA002098200A patent/CA2098200A1/en not_active Abandoned
- 1991-12-16 WO PCT/US1991/009463 patent/WO1992011038A1/en not_active Application Discontinuation
- 1991-12-16 JP JP4503722A patent/JPH06504059A/ja active Pending
- 1991-12-16 EP EP92903625A patent/EP0563294A1/en not_active Withdrawn
- 1991-12-20 IE IE451391A patent/IE914513A1/en not_active Application Discontinuation
- 1991-12-20 PT PT99912A patent/PT99912A/pt not_active Application Discontinuation
- 1991-12-20 NZ NZ241097A patent/NZ241097A/en unknown
- 1991-12-20 MY MYPI91002365A patent/MY107811A/en unknown
- 1991-12-20 MX MX9102753A patent/MX9102753A/es unknown
- 1991-12-21 CN CN91109058A patent/CN1063221A/zh active Pending
-
1993
- 1993-06-16 NO NO93932212A patent/NO932212L/no unknown
- 1993-06-18 FI FI932842A patent/FI932842A/fi not_active Application Discontinuation
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4221778A (en) * | 1979-01-08 | 1980-09-09 | Pennwalt Corporation | Prolonged release pharmaceutical preparations |
EP0171528A2 (en) * | 1984-07-18 | 1986-02-19 | Pennwalt Corporation | Controlled release pharmaceutical preparations |
EP0294103A1 (en) * | 1987-06-02 | 1988-12-07 | Takeda Chemical Industries, Ltd. | A sustained-release preparation and production thereof |
EP0367746A2 (en) * | 1988-11-02 | 1990-05-09 | Richardson-Vicks, Inc. | Sustained release drug-resin complexes |
Non-Patent Citations (1)
Title |
---|
Chemical Abstracts, vol. 101, no. 8, August 1985, (Columbus, Ohio, US), L.P. AMSEL et al.: "Recent advances in sustained release technology utilizing ion exchange polymers", see page 303, abstract no. 60082s, & PROC. - PHARM. TECH. CONF.'83, 251-66, see abstract * |
Cited By (16)
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US5731005A (en) * | 1993-08-13 | 1998-03-24 | Vitaphore Corporation | Hydrogel-based microsphere drug delivery systems |
US5932248A (en) * | 1993-11-18 | 1999-08-03 | Paragon Medical Limited | Controlled release preparations for cytotoxic or cytostatic drugs |
ES2097087A1 (es) * | 1994-08-01 | 1997-03-16 | Univ Sevilla | Sistema de liberacion controlada de morfina y otros farmacos solubles en agua por complejacion con sustancias polimericas. |
US6001392A (en) * | 1996-12-20 | 1999-12-14 | Warner-Lambert Company | Antitussive drugs delivered by ion exchange resins |
CZ301557B6 (cs) * | 1998-07-17 | 2010-04-14 | Bristol-Myers Squibb Company | Entericky povlecená farmaceutická tableta a zpusob její prípravy |
KR20020016069A (ko) * | 2000-08-24 | 2002-03-04 | 민경윤 | 마크로라이드계 항생제의 경구투여용 조성물 및 이의 제조방법 |
WO2005023217A3 (en) * | 2003-09-03 | 2005-09-09 | Mallinckrodt Inc | Granular sustained release preparation and production thereof |
AU2004270188B2 (en) * | 2003-09-03 | 2010-04-01 | Mallinckrodt Inc. | Granular sustained release preparation and production thereof |
WO2005023217A2 (en) * | 2003-09-03 | 2005-03-17 | Mallinckrodt Inc. | Granular sustained release preparation and production thereof |
AU2004270188B8 (en) * | 2003-09-03 | 2010-04-29 | Mallinckrodt Inc. | Granular sustained release preparation and production thereof |
US7790201B2 (en) | 2003-09-03 | 2010-09-07 | Mallinckrodt Inc. | Granular sustained release preparation and production thereof |
US8377480B2 (en) | 2003-09-03 | 2013-02-19 | Hi-Tech Pharmacal Co., Inc. | Granular sustained release preparation and production thereof |
EP2500016A1 (en) | 2011-03-18 | 2012-09-19 | Laboratorios Del. Dr. Esteve, S.A. | Doxylamine resinate complex |
WO2012126770A1 (en) | 2011-03-18 | 2012-09-27 | Laboratorios Del Dr. Esteve, S.A. | Doxylamine resinate complex |
WO2015076821A1 (en) * | 2013-11-22 | 2015-05-28 | Tris Pharma, Inc. | Novel clonidine formulation |
US11918689B1 (en) | 2020-07-28 | 2024-03-05 | Tris Pharma Inc | Liquid clonidine extended release composition |
Also Published As
Publication number | Publication date |
---|---|
CZ119793A3 (en) | 1994-01-19 |
NZ241097A (en) | 1994-11-25 |
HU9301819D0 (en) | 1993-09-28 |
CN1063221A (zh) | 1992-08-05 |
SK59493A3 (en) | 1993-11-10 |
FI932842A0 (fi) | 1993-06-18 |
MX9102753A (es) | 1992-06-30 |
NO932212D0 (no) | 1993-06-16 |
NO932212L (no) | 1993-08-20 |
IE914513A1 (en) | 1992-07-01 |
CA2098200A1 (en) | 1992-06-21 |
AU663695B2 (en) | 1995-10-19 |
HUT74642A (en) | 1997-01-28 |
FI932842A (fi) | 1993-06-18 |
AU9168791A (en) | 1992-07-22 |
BR9107173A (pt) | 1993-11-16 |
PT99912A (pt) | 1993-01-29 |
MY107811A (en) | 1996-06-29 |
JPH06504059A (ja) | 1994-05-12 |
EP0563294A1 (en) | 1993-10-06 |
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