Oral cholestyramine formulation and use thereof

A method for treating bile acid malabsorption in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of an oral formulation comprising:

• a) a plurality of extruded and spheronized pellets, each extruded and spheronized pellet comprising cholestyramine and
• i. at least 7% w/w of a vinylpyrrolidone-based polymer;
• or
• ii. a combination of at least 6% w/w of a vinylpyrrolidone-based polymer and at least 2% w/w of an acrylate copolymer;
• or
• iii. a combination of at least 5% w/w of a vinylpyrrolidone-based polymer and at least 3% w/w of an acrylate copolymer;
• or
• iv. a combination of at least 6% w/w of a vinylpyrrolidone-based polymer, at least 1% w/w of an acrylate copolymer and at least 10% w/w microcrystalline cellulose;
• wherein the vinylpyrrolidone-based polymer is selected from the group consisting of copovidone, povidone, and combinations thereof;
• wherein the pellets exhibit a friability of less than 2.1% as measured using the European Pharmacopoeia 8.0, test 2.9.7;
• and
• b) a coating surrounding each extruded and spheronized pellet, wherein the coating is capable of targeting release of the cholestyramine in the colon.

A method for treating bile acid diarrhoea in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of an oral formulation comprising:

• a) a plurality of extruded and spheronized pellets, each extruded and spheronized pellet comprising cholestyramine and
• i. at least 7% w/w of a vinylpyrrolidone-based polymer;
• or
• ii. a combination of at least 6% w/w of a vinylpyrrolidone-based polymer and at least 2% w/w of an acrylate copolymer;
• or
• iii. a combination of at least 5% w/w of a vinylpyrrolidone-based polymer and at least 3% w/w of an acrylate copolymer;
• or
• iv. a combination of at least 6% w/w of a vinylpyrrolidone-based polymer, at least 1% w/w of an acrylate copolymer and at least 10% w/w microcrystalline cellulose;
• wherein the vinylpyrrolidone-based polymer is selected from the group consisting of copovidone, povidone, and combinations thereof;
• wherein the pellets exhibit a friability of less than 2.1% as measured using the European Pharmacopoeia 8.0, test 2.9.7;
• and
• b) a coating surrounding each extruded and spheronized pellet, wherein the coating is capable of targeting release of the cholestyramine in the colon.

A process for the preparation of coated extruded and spheronized pellets comprising:

• a) a plurality of extruded and spheronized pellets, each extruded and spheronized pellet comprising cholestyramine and
• i. at least 7% w/w of a vinylpyrrolidone-based polymer;
• or
• ii. a combination of at least 6% w/w of a vinylpyrrolidone-based polymer and at least 2% w/w of an acrylate copolymer;
• or
• iii. a combination of at least 5% w/w of a vinylpyrrolidone-based polymer and at least 3% w/w of an acrylate copolymer;
• or
• iv. a combination of at least 6% w/w of a vinylpyrrolidone-based polymer, at least 1% w/w of an acrylate copolymer and at least 10% w/w microcrystalline cellulose;
• wherein the vinylpyrrolidone-based polymer is selected from the group consisting of copovidone, povidone, and combinations thereof;
• wherein the pellets exhibit a friability of less than 2.1% as measured using the Eurpoean Pharmacopoeia 8.0, test 2.9.7;
• and
• b) a coating surrounding each extruded and spheronized pellet, wherein the coating is capable of targeting release of the cholestyramine in the colon,
• the process comprising the steps of:
• a) preparing the pellets in a method comprising:
• i) mixing the dry ingredients;
• ii) adding water, and optionally the acrylate copolymer, to obtain a wet mass;
• iii) extruding the wet mass;
• iv) spheronizing the extrudate;
• and
• v) drying the obtained extruded and spheronized pellets, wherein the pellets exhibits a friability of less than 2.1% as measured using the European Pharmacopoeia 8.0, test 2.9.7;
• and
• b) applying the coating to the extruded and spheronized pellets.