pH independent extended release pharmaceutical formulation
AssigneeAbbott Laboratories
InventorsKevin R. Engh, Yihong Qiu, Venkatramana M. Rao
Life of this patent
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Abstract
Pharmaceutical formulations of acidic pharmacologic agents which demonstrate improved uniformity of release over the wide range of pH values encountered between the stomach and intestinal tract comprise an acidic pharmacologic agent dissolved or dispersed in a matrix comprising about 10 weight percent to about 40 weight percent of a a neutral water-swellable hydrophilic polymer and 20 weight percent to about 50 weight percent of an acid-soluble polymer which swells in water at pH values above about 5. A particularly preferred formulation comprises divalproex sodium. Also disclosed are pre-tablet granulations and process for preparing both the pre-tablet granulation and the tablet unit dosage form.
Claims30
A pharmaceutical composition comprising a therapeutically effective amount of an acidic pharmacologic agent dissolved or dispersed in a polymer matrix comprising
- a) from about 10 weight percent to about 40 weight percent of a pharmaceutically acceptable neutral, water-swellable, hydrophilic polymer, and
- b) from about 15 weight percent to about 50 weight percent of a pharmaceutically acceptable acid soluble polymer which is water swellable above about pH 5,
- all percentages based upon the total weight of the formulation.
A pharmaceutical composition comprising a therapeutically effective amount of an acidic pharmacologic agent dissolved or dispersed in a matrix comprising from about from about 10 weight percent to about 40 weight percent of a pharmaceutically acceptable neutral water-swellable cellulosic polymer and from about 15 weight percent to about 50 weight percent of an acid-soluble polymer comprising a dialkylaminoalkyl-modified methacrylate polymer which is water swellable above about pH 5, all percentages based upon the total weight of the composition.
A pharmaceutical composition comprising a therapeutically effective amount of an acidic pharmacologic agent dissolved or dispersed in a matrix comprising from about 10 weight percent to about 40 weight percent of a neutral water-swellable cellulosic polymer and from about 15 weight percent to about 50 weight percent of an acid-soluble dialkylaminoalkyl-modified methacrylate polymer which swells in water above about pH 5, all weight percentages based upon the total weight of the composition.
A pharmaceutical dosage form comprising a therapeutically effective amount of divalproex sodium dissolved or dispersed in a matrix comprising from about 10 weight percent to about 40 weight percent of a neutral water-swellable cellulosic polymer and from about 20 weight percent to about 50 weight percent of an acid-soluble dialkylaminoalkyl-modified methacrylate polymer which is water swellable at pH values above 5, all percentages based upon the total weight of the dosage form.
A dry granular composition suitable for compressing into a tablet dosage form, comprising particles containing an acidic pharmacologic agent dissolved or dispersed in a matrix comprising from about 10 weight percent to about 40 weight percent of a neutral, water swellable hydrophilic polymer and from about 20 weight percent to about 50 weight percent of an acid soluble polymer which is water swellable at pH values above about 5, all weight percentages based upon the total weight of the granular composition.
A process for preparing a granular pharmaceutical composition suitable for pressing into tablets comprising the steps of
- a) dry blending a mixture of from about 5 weight percent to about 50 weight percent of an acidic pharmacologic agent, from about 20 weight percent to about 40 weight percent of a neutral, water-swellable hydrophilic polymer, and from about 20 weight percent to about 50 weight percent of an acid soluble polymer which is water-swellable at pH values above about 5 to form a uniform mixture;
- b) wet granulating the dry uniform mixture from step a);
- and
- c) drying and sizing the wet granules from step b),
- wherein all percentages are based upon to total weight of the granulation.
A method of preparing a controlled release tablet dosage form of an acidic pharmacologic agent comprising the steps of
- a) dry blending a mixture of from about 5 weight percent to about 50 weight percent of an acidic therapeutic agent, from about 20 weight percent to about 40 weight percent of a neutral, water-swellable hydrophilic polymer, from about 20 weight percent to about 50 weight percent of an acid soluble polymer which is water-swellable at pH values above about 5 to form a uniform mixture;
- b) wet granulating the dry uniform mixture from step a);
- c) drying and sizing the wet granules from step b);
- and
- d) compressing the blended granules of step c) under a force ranging between about 2000 lbf (about 8.9.times.10.sup.3 Newtons) and about 10,000 lbf (about 4.45.times.10.sup.4 Newtons).
Dependencies are inferred from the claim text.