Abstract: Soft capsules coated with an enteric coating comprising a 1:1 copolymer of methacrylic acid and methyl or ethyl acrylate or methyl or ethyl methacrylate and a plasticizer without need for a subcoating and optionally additionally coated with a protective coating comprising hydroxypropyl methylcellulose or hydroxypropyl cellulose or a mixture thereof and a plasticizer and method of preparation thereof are disclosed.

Abstract: Freeze-dried polymer latices, which can be reconstituted in water to give aqueous polymer dispersions having high polymer solids content, are described. The reconstituted polymer dispersions are useful in preparing sustained-release drug formulations, particularly of water-soluble drugs, by the wet granulation method without over wetting.

Abstract: Controlled release pharmaceutical beads are provided having a multi-layered core and a multi-layered periphery. The core contains at least (A) an inner portion having a suitable organic acid and (B) a sustainably-acid-releasing coating thereover. The periphery contains at least (A) an inner portion having a mixture of at least (i) a pharmaceutical compound and (ii) a surface-active agent, and (B) a sustainably-drug-releasing exterior coating.

Abstract: An oral pharmaceutical composition comprises a core containing a drug, a first inner layer coating on the core which contains a drug, and a second inner layer coating on the first inner layer coating which also contains drug. This oral pharmaceutical composition is used especially for treating intestinal diseases.

Abstract: Pharmaceutical delivery systems containing 7-dimethyl-6-deoxy-6-demethyltetracycline or a non-toxic acid addition salt thereof comprising mixtures or separate administration units of pH sensitive polymer coated spherical granules adapted to release the minocycline in a medium having a pH of in the range of from about 4.0 to about 7.5 and coated or uncoated quick release granules adapted to release minocycline in a medium having a pH of less than about 3.9 or minocycline powder, pH adapted multi-coated compositions and oral dosage unit form liquids, capsules or tablets containing the above are provided. These systems and formulations provide at least minimum therapeutic blood levels of minocycline for at least about 24 hours when administered to a subject only once-a-day. Methods for the preparation of the systems and formulations are provided as well.

Abstract: A controlled-release organic nitrate formulation for once-per-day oral administration is provided by spheres having a core which includes an organic nitrate, and a membrane surrounding the core composed of a pharmaceutically acceptable, film forming polymer. The film forming polymer is effective to permit release of the organic nitrate from the spheres, over a daily dosing period, at a rate that achieves a therapeutically effective level of the organic nitrate, while effecting a drug holiday towards a latter portion of the daily dosing period so as not to induce tolerance.

Abstract: An extended-release galenical form of Diltiazem or a pharmaceutically acceptable salt thereof, which comprises beads containing said Diltiazem or a pharmaceutically acceptable salt thereof as an active ingredient and a wetting agent, said beads being coated with a microporous membrane comprising at least a water-soluble or water-dispersible polymer or copolymer and a pharmaceutically acceptable adjuvant.

Abstract: A process for encapsulating a wide variety of target materials, including both hydrophilic and hydrophobic materials, employs condensation of two reactive compounds to form shells around core phase particles including target material dispersed in a continuous phase. One of the reactive compounds has at least two active methylene functional groups per molecule, the other being an active methylene-reactive crosslinking agent. Either type of the reactive compounds can be dispersed in the continuous phase, the other being dispersible in the core phase. Applications include controlled release microencapsulation of agriculture chemicals and biocides.

Abstract: Sustained release microcapsules including a water soluble drug and an organic basic substance as a drug retaining substance of this invention not only have a high rate of incorporation (trapping rate), but also show little initial release so that they can be administered safely and bring about persistent, stable sustained release.

Abstract: Pharmaceutical delivery systems containing 7-dimethyl-6-deoxy-6-demethyltetracycline or a non-toxic acid addition salt thereof comprising mixtures of a minor proportion of slow-release blended polymer coated spherical granules adapted to release part of the minocycline in a medium having a pH of below 3.9 and the rest in the range of from about 4.0 to about 7.5 and a major proportion of coated or uncoated quick-release granules adapted to release minocycline in a medium having a pH of less than about 3.9 and oral dosage unit form capsules containing the above are provided. These systems and formulations provide enhanced therapeutic blood levels of minocycline for at least about 24 hours when administered to a subject only once-a-day, regardless of whether the patient is fed or fasted. Methods for the preparation of the systems and formulations are provided as well.

Abstract: Disclosed are gastric acid-resistant polymer-coated buffered-bile acid compositions, process for their preparations and methods of treating digestive disorders, impaired liver function, autoimmune diseases of the liver and biliary tract, prevention of colon cancer following cholecystectomy, cystic fibrosis, dissolving gallstones and regulating dietary cholesterol absorption by administering said compositions to a mammal in need of such treatment.

Abstract: A coating material for controlling drug release, useful for long acting formulations--e.g. for once-a-day administration, and to a long acting granular composition comprising a drug (especially one conventionally difficult to prepare in long acting form) coated with the coating material. This composition may be mixed with other granular drug formulations. The drug-release controlling coating material comprising, in a specific ratio, one specific water-insoluble and low water-permeability polymers and two materials differing from each other in the pH-dependency of their solubility (pH-dependent polymer-materials).

Abstract: Solid dosage forms of bioactive materials for parenteral administration such as porcine or bovine somatotropin pellets intended for subcutaneous implantation to improve food production of farm animals are coated with polyvinyl alcohol to extend the release characteristics of the material. The polyvinyl alcohol preferably has a molecular weight of from about 20,000 to 100,000, a degree of hydrolysis of at least about 98%, and is applied from an aqueous solution by spray coating to form a continuous uniform covering of from about 3 to 25 ug PVA/mm.sup.2 surface area of pellet.

Abstract: There is disclosed a process for the extraction of volatile solvents entrained in a polymer-based pharmaceutical composition designed for sustained release of drug over an extended period of time prepared in microcapsule form wherein the composition comprises at least one hormonally active water-soluble polypeptide in an effective amount greater than a conventional single dose and a biocompatible, bioerodable encapsulating polymer, which process comprises the steps of contacting the composition to a stream of dense gas, that is, pressurized gas and then removing the dense gas, and volatile solvents contained therein, extracted from the pharmaceutical composition.

Abstract: In microcapsules with a polymeric capsule wall, the polymer of the capsule wall comprises thermolabile predetermined breaking points in the form of hexamethylenetetramine or acetaldehyde ammonia derivatives in order to facilitate release of the capsule contents (various active substances, such as example, dyes, medicaments, developers, curing agents, flameproofing agents) in a specific manner by exposure to heat.

Abstract: An in vivo method is described for treating a subject for periodontal disease by placing a mixture of a glyceride composition and a therapeutic agent in the periodontal pocket of subject such that the therapeutic agent is released in a sustained manner. The glyceride composition is selected such that the mixture of the glyceride composition and the therapeutic agent is capable of forming a gel in the environment of the periodontal pocket. Also described is a sustained release delivery system comprising the mixture of the glyceride composition and therapeutic agent.

Abstract: An enteric coated pharmaceutical composition is provided which includes a medicament which is sensitive to a low pH environment of less than 3, such as pravastatin, which composition is preferably in the form of pellets which includes an enteric coating formed of neutralized hydroxypropylmethyl cellulose phthalate, plasticizer and anti-adherent. The so-coated pellets have good resistance to deterioration at pH less than 3 but have good drug release properties at greater than 3.

Abstract: A sustained-release pranoprofen preparation is disclosed. The preparation comprises an effective amount of pranoprofen and one or more sustained-release components selected from the group consisting of oily components, water-soluble components, water-insoluble components, and intestinally soluble components. It controls release of pranoprofen and lowers the maximum pranoprofen concentration in blood, maintaining its concentration in blood at a certain level for a long period of time. It reduces risks of side effects and can effectively treat diseases with dosing once or twice a day.

Abstract: A process for encapsulating a wide variety of target materials, including both hydrophilic and hydrophobic materials, employs condensation of two reactive compounds to form shells around core phase particles including target material dispersed in a continuous phase. One of the reactive compounds has at least two active methylene functional groups per molecule, the other being an active methylene-reactive crosslinking agent. Either type of the reactive compounds can be dispersed in the continuous phase, the other being dispersible in the core phase. Applications include controlled release microencapsulation of agriculture chemicals and biocides.

Abstract: A diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble synthetic polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer being effective to permit release of diltiazem from the pellet at a rate allowing controlled absorption thereof over a twelve hour period following oral administration. The pellet has a dissolution rate in vitro which when measured in a dissolution apparatus (Paddle) according to U.S. Pharmacopoeia XXI in 0.05 M KCl at pH 7.0 results in not more than 35% of the total diltiazem being released after 2 hours of measurement.

Abstract: Sugar or sugar/starch beads coated with a first coating of a drug, for example 1,2-dihydro-6-(lower alkyl)-2-oxo-5-(4-pyridinyl)-nicotinonitrile (milrinone), hydroxypropyl methylcellulose or hydroxypropyl cellulose and a plasticizer selected from triacetin, diacetylated monoglycerides, glycerin, propylene glycol, polyethylene glycol, diethyl phthalate and triethyl citrate or a mixture of two or more thereof and a second coating of high-viscosity ethylcellulose, low-viscosity ethylcellulose, hydroxypropyl cellulose, polyvinyl acetate phthalate and a plasticizer selected from diacetylated monoglycerides and triacetin or a mixture thereof and optionally coated with additional first coating and capsules filled therewith and method of preparation thereof are disclosed.

Abstract: A pharmaceutical composition capable of being disintegrated in an acidic environment, which comprises calcium polycarbophil and 1 to 80% by weight of a cellulose derivative such as carboxymethylcellulose or low substituted hydroxypropylcellulose based on the calcium polycarbophil. The pharmaceutical composition in a form of a tablet, a capsule, or granules is useful as a bulk-forming laxative or an antidiarrheic agent since it can be disintegrated readily in the stomach and form a complete dispersion of polycarbophil in the digestive tract.

Abstract: Controlled release medicament pellets comprisinga) a core which contains as active ingredient a compound of the formula ##STR1## or a compound from the group of 3-(4-fluorophenylsulphonamido)-1,2,3,4-tetrahydro-9-carbazole propanoic acid or 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzisothiazol-3 (2H)-one 1,1-dioxide monohydrochloride, an intensive disintegrating agent, a wetting agent and a binder,b) a double layer which controls release comprising(b1) an acrylic-based outer undigestible water-permeable lacquer layer, and(b2) an inner jacket layer comprising a hydrophobic additive and hydroxypropylcellulose of type M or H.

Abstract: The present invention relates to a pharmaceutical pellet composition having a core element including at least one highly soluble active ingredient and a core coating which is partially soluble at a highly acidic pH. The pharmaceutical composition provides a slow release of active ingredient at a highly acidic pH and provides a constant, relatively faster rate of release at a more alkaline pH such as that of the intestine. Oral administration of the pharmaceutical pellet composition of the present invention to a patient is effective to deliver to the blood levels of active ingredient within the therapeutic range and to maintain such levels over an extended period of time.

Abstract: A preparation method of sodium diclofenac enteric-coated microcapsules by spray drying technique comprising the steps of(a) dissolving sodium diclofenac in an appropriate amount of distilled water;(b) adding an effective amount of excipients to the above solution to form a suspension;(c) adding methacrylic acid-ethyl acrylate copolymers (Eudragit L 30D) and polyethyleneglycol 6000 (PEG 6000) as the enteric-coating material to form a slurry;(d) atomizing the slurry to form spray-dried powder;(e) mixing the spray-dried powder with a mixture of microcrystalline cellulose (neocel) and pregelatinized starch (flo-starch); and(f) compressing the powder mixture into a microdispersed enteric tablet.The spray drying technique could be easily performed to prepare the enteric-coated microcapsules with aqueous latex polymer dispersion such as Eudragit L 30D as an enteric-coating polymer.

Abstract: A pH-dependent sustained release pharmaceutical pellet composition and a method of administering the same to a patient at a predetermined dosage and interval, said pellet composition comprising: a core element containing a therapeutically effective amount of theophylline, xanthine or a derivative thereof as the active ingredient and a coating on said core element which comprises the following components:(a) at least 40% of a matrix polymer which is insoluble at a pH of from 1 to 7.5 and contributes to the control of the rate of release of the active ingredient in the stomach and intestines;(b) from 1 to 30% of an enteric polymer which is substantially insoluble at a pH of from 1 to 4, sufficient to delay the release of the active ingredient in the stomach, but which is soluble at a pH of from 6 to 7.

Abstract: The invention relates to an oral pharmaceutical multiple units formulation made up of individual cores containing a pharmacologically active substance, the cores being provided with a coating consisting essentially of a polymer that is insoluble in, impermeable to and non-soluble in water and in gastrointestinal fluids, and a water-soluble pore-creating substance, which is randomly distributed in said polymer, whereby said coated cores form units providing an essential zero order diffusion controlled release rate of said active substance. The invention also comprises a method of preparing these formulations.

Abstract: Orally administrable pharmaceutical preparation containing an active ingredient to be released in the lower part of the gastrointestinal tract, i.e. in the large intestine, and especially colon, consisting of a core containing a therapeutically active substance and coated with three protection layers at different solubility. The manufacturing and the use of these preparations are also described.

Abstract: A formulation comprising captopril within an enteric or delayed release coated pH stable core combined with additional captopril that is available for immediate release following administration.

Abstract: A pharmaceutical composition which comprises particles of a finely divided pharmaceutically acceptable water soluble diluent coated with microcrystalline particles of nifedipine, the majority of which have a particle size of 100 micrometers or less in the presence of polyvinyl-pyrrolidone, the polyvinylpyrrolidone being present in an amount of from 10 to 90% by weight based on the weight of the nifedipine. The incorporation of polyvinylpyrrolidone in an amount of less than the amount of nifedipine significantly slows the dissolution of nifedipine from the finished solid dosage form.

Abstract: Particles of active substance are encapsulated by spraying them with a thermoplastic silicone copolymer in solution in an organic solvent or in an aqueous dispersion or emulsion and removing the solvent or water by drying with hot air. The spraying/drying process employed is, for example, the Wurster process. The copolymer employed can be made up of a succession of polydiorganosiloxane segments or blocks and of organic segments or blocks (polyesters, polyethers, polyurethanes, polystyrenes, and the like). It can also be a polydiorganosiloxane grafted with organic chains. The active substance is in the form of particles with a particle size of between 50 .mu.m and 5 mm. It may be a catalyst, a perfume, a colorant, a cosmetic product, a medication, a plant-protection product, plant seeds, and the like.The invention is especially useful for controlling the release of active substance in an aqueous medium.

Abstract: A controlled release formulation comprising an adsorbate of a mixture of a pharmaceutically useful active ingredient and an inactive substance adsorbed on a cross-linked polymer. The inactive substance is selected to modify the dissolution of the active ingredient from the cross-linked polymer in vivo.

Abstract: A controlled-release organic nitrate formulation for once-per-day oral administration is provided by spheres having a core which includes an organic nitrate, and a membrane surrounding the core composed of a pharmaceutically acceptable, film forming polymer. The film forming polymer is effective to permit release of the organic nitrate from the spheres, over a daily dosing period, at a rate that achieves a therapeutically effective level of the organic nitrate, while effecting a drug holiday towards a latter portion of the daily dosing period so as not to induce tolerance.

Abstract: A sustained-release pharmaceutical composition which comprises microparticles comprising an active principle, said microparticles being coated with a coating mixture comprising ethyl cellulose and an acrylic resin which is a polymerizate of acrylic and methacrylic ester, having a molecular weight of at least 100,000 and comprising units of formula: ##STR1## wherein: R.sub.1 is hydrogen or methyl,R.sub.2 is methyl or ethyl,R.sub.3 is methyl; andR.sub.4 is --CH.sub.2 --CH.sub.2 N(CH.sub.3).sub.3 Clthe resin containing 5% of trimethylammonium methacrylate chloride units by weight.

Abstract: A polymeric complex composition comprising a reaction complex formed by the interaction of a polycarbophil component with alginic acid or a salt thereof, said interaction being performed in the presence of a divalent cation and in the presence of an active agent selected from the group consisting of medicinal agents and cosmetic agents. There is also described a method of controlled release treatment comprising the steps of providing such a polymeric complex and an effective amount of an active agent selected from the group consisting of medicinal agents and cosmetic agents contained within said complex, and contacting an area of skin or mucous membrane to be treated with said composition for a sufficient period of time allow a therapeutically effective amount of said active agent to be released from the complex.

Abstract: Controlled release compositions comprising calcium polycarbophil and an active agent selected from the group consisting of medicinal agents, breath fresheners, and flavors, and a method of controlled release of such an active agent.

Abstract: A sustained-release pH independent pharmaceutical preparation having multi-units of microparticles comprising a granular drug which is less soluble at low pH and more soluble at high pH. The granular drug is surrounded by or admixed with a pH controlled material formed from at least one polymer that is hydrophilic at low pH and hydrophobic at higher pH and is in a ratio with the granular drug such that the resulting sustained-release pharmaceutical preparation is independent from the pH environment. The resulting sustained-release pH independent pharmaceutical preparation allows a uniform release of drug for a period of at least 12 to 24 hours. In an alternative embodiment, the drug may be more soluble at low pH and less soluble at higher pH and the pH controlled material formed from at least one polymer that is hydrophobic at low pH and hydrophilic at higher pH.

Abstract: The invention relates to an advantageous oral administration from the disodium pamidronate in capsules. These capsules are filled with double-coated granules. The inner coating is hydrophilic and elastic, and the outer coating is gastric juice-resistant and intestinal juice-soluble. The granules are distinguished by good gastric compatibility.

Abstract: A pharmaceutical composition useful for treating hypercholesterolemia comprising a bile acid sequestrant resin such as cholestyramine and cholestipol maintained in a semipermeable water-insoluble material; wherein said semipermeable material enables bile acids from the digest tract to contact and bind to said resin while preventing substances having a higher molecular weight than bile acids from contacting said resin material. A method for treating hypercholesterolemia using the inventive composition is also disclosed.

Abstract: A pharmaceutical preparation comprising drug micropellets containing a drug coated on a core material wherein each pellet ranges in size from about 70 microns to 750 microns and wherein each micropellet is coated with a controlled release coating.

Abstract: A rapid-releasing oral particle pharmaceutical preparation with its unpleasant taste masked comprising a core and a film layer coating the core, the core at least containing a drug having an unpleasant taste and a water-swelling agent, and the film layer at least containing ethylcellulose and a water-soluble substance, the amount of the drug in the core being at most 40% (based on the final particle preparation and so on), the amount of the water-swelling agent being about 35% to about 70%, the amount of ethylcellulose in the film layer being about 3 to about 11%, and the amount of the water-soluble substance being about 0.1 to about 0.8 times the weight of the ethylcellulose.

Abstract: A sustained release composition for releasing a biologically active compound into an aqueous liquid environment comprises a biologically active compound dispersed in a matrix which progressively erodes in contact with a liquid environment, the matrix having a melting point below the melting point of the biologically active compound, and the matrix comprising a mixture ofa.) 5% to 100% by weight of a solid water-dispersible polyether diol having a molecular weight from about 1000 to about 20,000, selected from the group consisting of polyethylene glycols and polyethylene oxide-polypropylene oxide block copolymers, andb.) 95 to 0% by weight of an erosion rate modifier which is an amphiphilic compound insoluble in the aqueous liquid.Dosage forms comprising the sustained release composition are prepared by molding, particularly by injection molding.

Abstract: A method of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a biocompatible excipient to form microcapsules having a size ranging from between approximately one micrometer to approximately ten micrometers and admnistering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immuity. Related compositions are also provided.

Abstract: The invention involves a granulating composition composed of an aqueous solution of magnesium sulfate heptahydrate and sodium hexametaphosphate. This composition can be used to prepare granules of ingredients for inclusion in any formulation for which rapid disintegration or dispersion are important factors. It is useful for tablets containing ingredients which are difficult to compress and is particularly useful for formulating swallowable tablets of a single non-soluble ingredient such as calcium carbonate. Disintegration times are markedly decreased.

Abstract: An ion exchange resin composition which is readily dispersible in water is provided. This resin composition comprises a granulated ion exchange resin, a pharmacologically active ingredient bound thereto with a sugar or sugar alcohol, and a sufficient amount of water, alcohol or aqueous alcohol to facilitate granulation. The invention further comprises a method for the preparation of such ion exchange resin composition.

Abstract: The present invention is a stabilized enteric-coated pharmaceutical dosage form and processes for the preparation thereof. Dissolution stability after storage of the dosage form under high stress conditions is improved by an enteric-coated dosage form having an enteric coating wherein the coating is of the acrylic resin kind of from 14 mg/cm.sup.2 to 24 mg/cm.sup.2 or an enteric coating wherein the coating is of the acetate kind of from 14 mg/cm.sup.2 to 24 mg/cm.sup.2 and having a second coating of hydrophilic coating for example, hydroxypropyl cellulose, hydroxymethyl cellulose or hydroxypropylmethyl cellulose.

Abstract: A process for microencapsulating bioactive substances in biocompatible polymers according to the phase-separation principle, wherein an excess of an ethyl or isopropyl ester of a straight-chain fatty acid having 12-18 carbon atoms is used as the hardening liquid, and the pharmaceutical compositions containing the microcapsules prepared by this process. Isopropyl myristate and isopropyl palmitate are preferred hardening liquids.

Abstract: An active principle microencapsulated in an envelope formed by interfacial polymerization of two non-miscible phases A and B, organic phase A comprising at least one water insoluble active principle which do not react with each other, a polyfunctional monomer a and a solvent for the active principle and aqueous phase B comprising a polyfunctional monomber b and a catalyst which allows a progressive diffusion of the active principle and protects the same from the environment.

Abstract: A method for treating azaribine-responsive diseases in patient's who exhibit severe pyridoxal phosphate depletion following the oral administration of azaribine comprises first encapsulating azaribine in a film-forming substance which is selectively soluble in the digestive juice of the intestines. The encapsulated azaribine is then orally administered to the patient in an amount effective for the treatment of the disease, preferably in an amount to provide from about 1.5 to about 15 grams of azaribine per square meter of patient body surface area per day.

Abstract: A magnetically responsive composition for the modulated, sustained administration of a biologically active substance, the composition being in the form of a body sized and shaped for placement in the environment of use, the environment including an aqueous fluid, the body comprising, in admixture, a first phase comprising a biocompatible, plastically deformable, polymeric matrix, the polymeric matrix being insoluble in the environment of use, a second phase having a biologically active substance distributed throughout the matrix to be released to the aqueous fluid outside the matrix, and a third phase comprising a magnetically responsive substance encapsulated within the matrix so that, upon exposure of the body to an oscillating magnetic field, the rate of release of the biologically active substance to the aqueous fluid is increased.