Proton pump inhibitor formulation
OwnerDaniel J. Cullen, Christopher Pelloni +1inventors
InventorsDaniel J. Cullen, Christopher Pelloni, theodore E. Burnell
Life of this patent
Estimating the term…
Abstract
Pharmaceutical capsule dosage forms of benzimidazole proton pump inhibitors are prepared by enclosing one or several enteric coated compressed cores in a capsule shell. The inventive formulations are stable and have higher bioavailability of the active ingredient relative to pellet and granule containing formulations.
Claims20
A delayed-release, pharmaceutical capsule dosage form, which comprises one or several enteric-coated, compressed cores encapsulated by a capsule shell, wherein the enteric coated compressed core consists essentially of a mixture of a pharmaceutically acceptable carrier and an pharmaceutically effective amount of a pharmaceutically active compound of the formula (I)
- 5
- wherein R1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R3 and R5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, or a pharmaceutically acceptable salt thereof;
- which mixture has been compressed at a pressure in the range from 350 to 1500 pounds to form a compressed core and the compressed core is directly coated with an effective release-delaying amount of an enteric coating.
A method of inhibiting the secretion of gastric acid in a mammalian subject which comprises administering to the subject a delayed-release, pharmaceutical capsule dosage form, which comprises one or more enteric-coated, compressed cores encapsulated by a capsule shell, wherein the enteric-coated compressed core consists essentially of a core which is a mixture of a pharmaceutically acceptable carrier and an effective amount of a pharmaceutically active compound of the formula (I)
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- wherein R1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R3 and R5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4;
- which mixture has been subjected to compression at a pressure in the range from 500 to 1200 pounds.
A process for preparing a enteric-coated, capsule dosage form containing a pharmaceutical effective amount of a compound of formula (I)
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- wherein R1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R3 and R5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4;
- which consists essentially of the steps of
- (i) compressing a mixture of a compound of formula (I) and a pharmaceutically acceptable carrier at a pressure in the range from 350 to 1500 pounds to form a compressed core which has a surface area to volume ratio of from 0.5 to 2.5 mm−1;
- (ii) coating the compressed core with an effective release-delaying amount of an enteric coating to form an enteric-coated compressed core;
- and
- (iii) encapsulating from 1 to 4 enteric-coated compressed cores in a capsule shell to form a delayed-release capsule dosage form containing a pharmaceutically effective amount of a compound of formula (I).
Dependencies are inferred from the claim text.