Abstract: The present invention relates to a composition and method of treating a patient by administering carbamazepine in a pharmaceutical dosage form capable of maintaining the patient's blood concentration at from about 4 .mu.g/ml to about 12 .mu.g/ml over at least a 12 hour period, where the blood concentration of carbamazepine does not vary by more than 60 percent.

Abstract: A programmed release pharmaceutical dosage form comprising a core, containing the active ingredient, coated by a hydrophobic layer is described.Such dosage forms release the active ingredient after a pre-established no-release interval which does not depend on physiological factors.

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: A large intestinal dissociative hard capsule comprising a capsule mainly composed of chitosan, the viscosity at 20.degree. C. of a solution obtained by dissolving the chitosan in an aqueous 1% by weight acetic acid solution being not higher than 100 cps and the degree of deacetilation of the chitosan being from 60 mol % to 98 mol %, having a coated layer of a polymer soluble in a liquid having pH of at least 5 on the surface of the capsule.

Abstract: The compound (S)-1-[(10-chloro-6,7-dihydro-4-oxo-3-phenyl-4H-benzo[a]quino-lizin-1-yl)c arbonyl]-3-ethoxypyrrolidine of the formula ##STR1## which has valuable pharmacological properties, is described. In particular, the compound of formula I has a non-sedating, hypnotic, that is, sleep-promoting, activity and can accordingly be used for the treatment of sleep disorders.

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: The pharmaceutical composition is intended in particular for the sustained and controlled release of an effective dose of a medicinal substance. It comprises, as a carrier for the medicinal substance, a biodegradable polymer or copolymer or a mixture of biodegradable polymers and/or copolymers derived from a dicarboxylic acid selected from the acids of the Krebs cycle, and from an aliphatic diol containing 4 carbon atoms or from cyclohexane-1,4-dimethanol.

Abstract: The invention provides a solid pharmaceutical dosage form comprising:(i) cimetidine; and(ii) antacid, wherein at least part of the antacid is in the form of granules comprising a freely water-soluble solid diluent, the antacid, and a rapidly swellable water-insoluble disintegrant.Compositions of this type overcome the problem of the reduced bioavailability of cimetidine which can occur when cimetidine is co-administered with antacids.

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: Pharmaceutical tablets having increased slipperiness and swallowability are provided. The enhanced swallowability is imparted by an overcoat of a low bloom gelatin, which overcoat has a lower coefficient of friction than other known coatings.

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 controlled release, solid, oral dosage form containing a 3-alkylxanthine, preferably theophylline, at least one hydrophilic or hydrophobic polymer, at least one wax having a melting point between 25.degree. and 90.degree. C. and between 3% and 10% (by weight) water.Preferably the dosage form is a tablet and the water content is between 4% and 9% (by weight). The amount of water present in the dosage form determines the rate of release of the 3-alkylxanthine.

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: 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: New galenic formulations with programmed release, to be administered by the oral route, containing as the active ingredient a drug selected from the non steroidal antiinflammatory, bronchodilator, vasodilator, cardiovascular and muscle relaxant drugs.

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: Slow-releasing granules which are characterized by coating the quick-releasing granules which comprise an active ingredient, polyvinyl pyrrolidone polymer and a disintegrator where the polymer distributes in high concentration on the surface area of the granules, with a polyacid enteric material to form a complex between the polyvinyl pyrrolidone polymer and the polyacid, and long lasting mixed granules which comprise the quick-releasing granules and the slow-releasing granules, thus showing increased bioavailability of the active ingredient and high stability sustained for a long period of time.

Abstract: The slow release preparation obtained by the method of the invention reduces the number of times the medicine needs to be taken per day, and also provides lower peaks of concentration in the blood after the medicine has been taken while simultaneously ensuring that the lowest concentration in the blood remains higher over a period of time.

Abstract: Preparation giving a controlled and extended release of both a dihydropyridine, e.g. felodipine and a .beta.-adrenoreceptor antagonist, namely metoprolol as well as a method for the manufacture of the new preparation.

Abstract: Combinations of calcium antagonists and lipid-lowering agents are suitable for controlling diseases.

Abstract: Mammals are brought to a specific state of immunization by administering an amount of an antigenic substance sufficient to elicit an immunization response to said mammal, said antigenic substance being incorporated within a shaped structure of a biocompatible matrix material.

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 lubricant, and a membrane surrounding the core comprising a multiplicity of sequentially applied and dried layers, each layer containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble, naturally occurring polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble 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 the diltiazem from the pellet at a rate allowing controlled absorption thereof over a twelve hour period following oral administration.

Abstract: A sustained absorption propranolol-containing pellet for oral administration comprises a core of propranolol or a pharmaceutically acceptable salt thereof and an organic acid embedded in a polymeric material in a multi-layer arrangement and an outer membrane which permits release of the propranolol at a controlled rate in an aqueous medium. The pellet has a dissolution rate in vitro in an aqueous medium, which when measured in a basket assembly according to U.S. Pharmacopoeia XX at 37.degree. C. and 75 r.p.m., is not more than 15% of the total propranol after 2 hours of measurement in a buffer solution at pH 7.5. Not more than 30% of the total propranolol is released after a total of 4 hours of measurement and not more than 63% of the total propranolol is released after a total of 6 hours.

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: A pharmaceutical dosage unit suitable for masking the unpleasant taste of orally administered pharmaceutical agents and which facilitates swallowing comprises a plurality of subdosage units disposed within a container. Each subdosage unit is a pellet with an inner core coated with an active pharmaceutical agent, a first layer surrounding the core comprising a biologically inert excipient or filler, and a second layer surrounding the first layer comprising a mixture of a cationic copolymeric acrylate resin and a basic compound. The container of the dosage unit may be orally ingestible in itself, such as an openable gelatin capsule, or may be a frangible packet which must be opened in order to orally administer the subdosage pellets to a patient.

Abstract: A controlled release pharmaceutical composition contains a number of spheroids, the spheroids containing a water-insoluble drug dispersed in a controlled release matrix. The matrix contains between 70% and 99.5% (by weight) of microcrystalline cellulose, between 0.5% and 4% (by weight) of a cellulose derivative and, optionally, up to 26% of a sugar or a sugar alcohol.The water insoluble drug must dissolve in water (pH 5) at 20.degree. C. to a concentration of less than 1.0 mg ml-1, preferably less than 0.5 mg ml-1. Preferred drugs are non-steroidal anti-inflammatory agents, especially fenprofen calcium, ibuprofen, ketoprofen, naproxen, diclofenac sodium, fenbufen, flurbiprofen, indomethancin, oxyphenbutazone, phenylbutazone or piroxicam.

Abstract: The invention relates to a novel galenic form of verapamil which show an excellent bioavailability. The novel galenic form comprises microgranules containing a verapamil addition salt with an acid, associated to at least one wetting agent. The microgranules are coated with a porous membrane constituted of a synthetic polymer associated to an adjuvant.

Abstract: The invention relates to nifedipine combination preparations, containing nifedipine with delayed release of active agent and a .beta.-blocker in each case in granulated form, and their pharmaceutical usage as a therapeutic agent in cardiovascular diseases.

Abstract: A medication and method for treating heartworms in dogs, which medication includes a time release capsule or tablet dosage structure which is characterized either by discrete elements (capsule) or an outer layer or layers (tablet) of vasoconstricting and bronchial dilating medications and an inner, time-released layer or pellets of diethylcarbamazine. The vasoconstrictors and bronchial dilators are designed to counteract life-threatening vasodilation and bronchial constriction resulting from the release of acetylcholine by the dog when the heartworms are attacked by the diethylcarbamazine. The solid dosage structure can be constructed by layering such vasoconstrictors and bronchial dilators as prednisone, ephedrine, digoxin and dextroamphetamine sulfate in separate layers or combining these ingredients in a single layer separated from the diethylcarbamazine by a time-release substance such as gelatin.

Abstract: The present invention provides for an oral drug delivery system based on a two phase liquid coacervate system prepared from water and one or more surfactants selected from anionic, cationic, amphoteric, and non-toxic surfactants, polysaccharides, synthetic polymers and polysorbates and their derivatives, and in which a pharmaceutical component is incorporated. The delivery system may be prepared in the form of a microemulsion as well as other forms including encapuslated microparticles. The claimed oral composition is useful to delivery oral dosage forms of drugs, their salts and derivatives thereof; biologicals, enzymes, and other pharmocologically active compositions. A method to prepare the oral drug delivery system is also disclosed.

Abstract: A therapeutic preparation consisting of three groups of spheroids containing an active medicinal substance. The first group of spheroids is uncoated and rapidly disintegrates upon ingestion to release an initial dose of medicinal substance a second group of spheroids is coated with a pH sensitive coat to provide a second dose and a third group of spheroids is coated with a pH independent coat to provide a third dose. A powder blend of active medicinal substance may be substituted for the first group of uncoated spheroids.The therapeutic preparation may be utilized as a mixture of groups of spheroids in a capsule.

Abstract: A delivery system is disclosed comprising a wall surrounding a lumen containing a plurality of dosage delivery devices. The wall is formed of an environment sensitive material that releases the dosage forms into the environment. The dosage forms comprise a semipermeable wall surrounding a compartment containing drug. A passageway through the semipermeable wall releases drug from the dosage form to the environment.

Abstract: A therapeutic preparation consisting of three groups of spheroids containing an active medicinal substance. The first group of spheroids is uncoated and rapidly disintegrates upon ingestion to release an initial dose of medicinal substance a second group of spheroids is coated with a pH sensitive coat to provide a second dose and a third group of spheroids is coated with a pH independent coat to provide a third dose. A powder blend of active medicinal substance may be substituted for the first group of uncoated spheroids.The therapeutic preparation may be utilized as a mixture of groups of spheroids in a capsule.

Abstract: A controlled absorption diltiazem formulation for oral administration comprises a pellet having a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid and a lubricant, and an outer membrane which permits release of diltiazem in an aqueous medium at a controlled rate which is substantially pH independent. The pellet has a dissolution rate in vitro, which when measured according to the Paddle Method of U.S. Pharmacopoeia XX, is not more than 10% of the total diltiazem after 2 hours of measurement in a buffered medium. Not more than 30% of the total diltiazem is released after a total of 4 hours measurement and not more than 40% of the total diltiazem is released after a total of 6 hours. 100% release is achieved after 12 hours, with a maximum of 80% of the total diltiazem being released after 8 hours.

Abstract: A controlled absorption methyldopa formulation for oral administration comprises a pellet having a core of methyldopa or a pharmaceutically acceptable salt thereof in association with an organic acid, and an outer membrane which permits release of methyldopa in an aqueous medium at a controlled rate which is substantially pH independent. The pellet has a dissolution rate in vitro, which when measured in a Basket Assembly according to U.S. Pharmacopoeia XX at 37.degree. C. and 75 r.p.m., is not more than 50% of the total methyldopa after one hour of measurement. Not more than 80% of the total methyldopa is released after a total of 3 hours of measurement and 100% release is achieved after a total of 7 hours.