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US 7,022,712 B2Granted
Solubilization of weak bases
AssigneeArizona Board of Regents on Behalf of the University of Arizona
InventorSamuel H. Yalkowsky
Life of this patent
Estimating the term…
Abstract
A pharmaceutical composition for administration to mammals comprising: a weak base compound having a compound pKa below about 7; an acidic buffer with a buffer pKa below 7; and optional pharmaceutically acceptable additives, wherein the composition has a pH below about 4 is provided. Preferred pharmaceutically active compounds are imidazole derivatives, pyridine derivatives, and aniline derivatives. The pharmaceutical compositions have greater water solubility than the weak base.
Claims24
A pharmaceutical composition comprising:
- a benzimidazole compound having a pKa below about 7 and having the formula:
- wherein X is hydrogen, halogen, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms;
- n is a positive integer of less than 4;
- Y is hydrogen, chlorine, nitro, methyl, ethyl or oxychloro;
- R is hydrogen, alkylaminocarbonyl wherein the alkyl group has from 3 to 6 carbon atoms or an alkyl group having from 1 to 8 carbons, and R2 is 4-thiazolyl, NHCOOR1 wherein R1 is an aliphatic hydrocarbon of less than 7 carbon atoms, or an alkyl group of less than 7 carbon atoms;
- or a compound of formula:
- where n is an integer from 1 to 3 and R is hydrogen, alkyl having from 1 to 7 carbon atoms, chloro, bromo, fluoro, oxychloro, hydroxy, sulfhydryl or alkoxy having the formula —O(CH2)yCH3 wherein y is an integer from 0 to 6;
- its pharmaceutically acceptable salt or its conventional prodrug of the hydroxy, amine or sulfhydryl group;
- an aqueous buffer solution of phosphoric acid and sugar with a pH between 1 and 2;
- and optionally pharmaceutically acceptable additives, wherein the composition has a pH below about 4.
7 more elements
A pharmaceutical composition comprising:
- (a) a benzimidazole compound having the formula:
- wherein X is hydrogen, halogen, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms;
- n is a positive integer of less than 4;
- Y is hydrogen, chlorine, nitro, methyl, ethyl or oxychloro;
- R is hydrogen, alkylaminocarbonyl wherein the alkyl group has from 3 to 6 carbon atoms or an alkyl group having from 1 to 8 carbons and R2 is 4-thiazolyl, NHCOOR1 wherein R1 is aliphatic hydrocarbon of less than 7 carbon atoms, or an alkyl group of less than 7 carbon atoms;
- or a compound of formula:
- where n is an integer from 1 to 3 and R is hydrogen, alkyl having from 1 to 7 carbon atoms, chloro, bromo, fluoro, oxychloro, hydroxy, sulfhydryl or alkoxy having the formula —O(CH2)yCH3 wherein y is an integer from 0 to 6;
- (b) a pharmaceutically acceptable carrier;
- and
- (c) an aqueous acidic buffer solution of phosphoric acid and sugar with a pH between 1 and 2.
7 more elements
A composition comprising:
- a compound of formula
- wherein X is hydrogen, halogen, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms;
- n is a positive integer of less than 4;
- Y is hydrogen, chlorine, nitro, methyl, ethyl or oxychloro;
- R is hydrogen, alkylaminocarbonyl wherein the alkyl group has from 3 to 6 carbon atoms or an alkyl group having from 1 to 8 carbons and R2 is 4-thiazolyl, NHCOOR1 wherein R1 is an aliphatic hydrocarbon of less than 7 carbon atoms, or an alkyl group of less than 7 carbon atoms;
- or a compound of formula:
- where n is an integer from 1 to 3 and R is hydrogen, alkyl having from 1 to 7 carbon atoms, chloro, bromo, fluoro, oxychloro, hydroxy, sulfhydryl or alkoxy having the formula —O(CH2)yCH3 wherein y is an integer from 0 to 6 having a compound pKa below about 7;
- an aqueous acidic buffer solution of phosphoric acid and sugar with a pH between 1 and 2;
- and
- optional pharmaceutically acceptable additives, wherein the composition has a pH below about 4.
7 more elements
A method of increasing the water solubility of a compound of formula
- wherein X is hydrogen, halogen, alkyl of less than 7 carbon atoms or alkoxy of less than 7 carbon atoms;
- n is a positive integer of less than 4;
- Y is hydrogen, chlorine, nitro, methyl, ethyl or oxychloro;
- R is hydrogen, alkylaminocarbonyl wherein the alkyl group has from 3 to 6 carbon atoms or an alkyl group having from 1 to 8 carbons and R2 is 4-thiazolyl, NHCOOR1 wherein R1 is an aliphatic hydrocarbon of less than 7 carbon atoms, or an alkyl group of less than 7 carbon atoms;
- or a compound of formula:
- where n is an integer from 1 to 3 and R is hydrogen, alkyl having from 1 to 7 carbon atoms, chloro, bromo, fluoro, oxychloro, hydroxy, sulfhydryl or alkoxy having the formula —O(CH2)yCH3 wherein y is an integer from 0 to 6 having a compound pKa below about 7, comprising contacting said compound with an aqueous acidic buffer solution of phosphoric acid and sugar with a pH between 1 and 2, forming a composition, and optionally adding pharmaceutically acceptable additives, wherein the composition has a pH below about 4.
3 more elements
Dependencies are inferred from the claim text.