Fmc Corporation

R.p.scherer Technologies, Inc.

Mutual Pharmaceutical Company, Inc.

Elite Laboratories, Inc.

David F Erkoboni

Ronald S Vladyka

Pamela R Stergios

Charanjit R Behl

Thomas A Wheatley

Kristin Anne Arnold

Gandha V Naringrekar

Christopher C Dick

Gary Bubb

Christopher A Sweriduk

Andrew Favara

Howard J Stamato

Victor L King

Scott A Fiore

Marc S Karetny

Aspects of the present invention are directed to abuse resistant oral dosage forms comprising a compressed microtablet that is coated with a water-retardant polymer. Additional aspects of the present invention are directed to an oral dosage form comprising an opioid agonist and at least one compressed microtablet coated with a water retardant polymer. The compressed microtablet may comprise an opioid antagonist.

Abuse resistant oral dosage forms

The present invention includes a controlled-release composition having a matrix. The matrix contains a pharmaceutically effective amount of an active agent or a pharmaceutically acceptable salt, solvate, ester, and/or prodrug thereof, an ionic non-gelling matrix polymer, and a pH modifier. The ionic non-gelling matrix polymer is practically insoluble and unswellable at a first aqueous fluid pH and is soluble at a second aqueous fluid pH. The pH modifier is present in an amount to control the release of the active agent from the composition. The controlled-release composition is substantially free of a gelling or swellable excipient. The present invention also provides methods of making and using the controlled-release compositions.

Controlled-release formulations, method of manufacture, and use thereof

The present invention includes a controlled-release composition having a matrix. The matrix contains a pharmaceutically effective amount of an active agent or a pharmaceutically acceptable salt or solvate thereof, an ionic non-gelling matrix polymer, and a pH modifier. The ionic non-gelling matrix polymer is practically insoluble and unswellable at a first aqueous fluid pH and is soluble at a second aqueous fluid pH. The pH modifier is present in an amount to control the release of the active agent from the composition. The controlled-release composition is substantially free of a gelling or swellable excipient and does not contain a functional coating or a lipophilic component. The present invention also provides methods of making and using the controlled-release compositions.

Granulation of microcrystalline cellulose with a granulating fluid consisting of water and a water-miscible, volatile, polar organic solvent yields porous granules which are comprised of particles that are larger than the ungranulated microcrystalline cellulose. This granulated microcrystalline cellulose is capable of cushioning controlled release particles and barrier coated particles from the compression forces used in tableting, thereby maintaining the physical integrity of the components of the tablet.

Microcrystalline cellulose cushioning granules

The present invention provides a method for preparing a spray-dried, compressible granular formulation for preparing pharmaceutical tablets in which essentially water-insoluble, acidic, amphoteric, and basic pharmaceutically active agents are converted to more water-soluble salts which are granulated with hydrolyzed cellulose, drug-containing slurries, the resulting granulations, capsules containing granulations, and pharmaceutical tablets compressed from such granules. In these formulations there is employed from 1% to 85% by weight of the pharmaceutically active agent and its salt form, from 5% to 99% of hydrolyzed cellulose, based on the dry weight of the granulation, and optionally, conventional granulation and/or tableting additives such as surfactants, disintegrants, and antiadherents/flow aids. Said tablets have significantly increased dissolution of the pharmaceutically active agent at the pH of the gastrointestinal tract in comparison with the unconverted free pharmaceutically active agent.

Hydrolyzed cellulose granulations of salts of drugs

A formulation of a sparingly water-soluble, crystalline pharmaceutically active agent wherein the active agent is converted to and stabilized in its amorphous form as a solid solution of a normally hydrophobic vehicle is described. The amorphous state is stabilized by the composition of the formulation, providing long shelf life of the improved composition. This stabilized formulation also provides increased solubility and bioavailability of the active agent. Solutions of the active agent are stabilized by the composition, preventing recrystallization and precipitation of the less soluble, crystalline form of the active agent from aqueous solutions thereof.

Aqueous solubility pharmaceutical formulations

Method of making granular pharmaceutical vehicle

The present invention provides a method for preparing a spray-dried compressible granular formulation for preparing pharmaceutical tablets in which hydrolyzed cellulose is used as a granulation aid, the resulting granulations, and pharmaceutical tablets compressed from such granules. In these formulations there is employed from 1 to 97% by weight pharmaceutical active, from about 3 to 99% by weight hydrolyzed cellulose, based on the dry weight of the granulation, and optionally conventional granulation and/or tableting additives such as surfactants, disintegrants and antiadherents/flow aids.

Hydrolyzed cellulose granulations for pharmaceuticals

A particulate co-processed unattrited microcrystalline cellulose:hydrocolloid composition wherein the respective components are present in a weight ratio of from about 99:1 to 70:30. The composition is useful as a spheronizing agent for producing spheroids of uniform size and sphericity and having high drug loadings. The composition is produced by drying a slurry of the microcrystalline cellulose in an aqueous solution of the hydrocolloid. The preferred hydrocolloid is methylcellulose.

Microcrystalline cellulose spheronization composition

A solid dosage form, such as a pharmaceutical tablet, containing a rapidly hydratable konjac glucomannan sustained release excipient such as clarified konjac, cryogenically ground konjac and plasticized konjac. The method of making the tablets by compressing excipient and pharmaceutically active ingredient as dry powders.

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Pennington, NJ, United States of America

David F Erkoboni