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.
Claims34
A pharmaceutical composition for administration to mammals comprising:
- a pharmaceutically active weak base compound having a compound pKa below about 7;
- an acidic buffer having a buffer pKa below about 7;
- and
- optional pharmaceutically acceptable additives, wherein the composition has a pH below about 4.
A pharmaceutical composition comprising:
- a benzimidazole derivative having a pKa below about 7 and having the formula:
- 19
- 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;
- an acidic buffer having a buffer pKa below about 7;
- and
- optional pharmaceutically acceptable additives, wherein the composition has a pH below about 4.
A method of increasing the water solubility of a pharmaceutically active weak base compound having a compound pKa below about 7, comprising contacting said compound with an acidic buffer having a buffer pKa below about 7, forming a composition, and
- optionally adding pharmaceutically acceptable additives, wherein the composition has a pH below about 4.
A pharmaceutical composition comprising:
- (a) a benzimidazole derivative having the formula:
- 22
- 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;
- (b) a pharmaceutically acceptable carrier;
- and
- (c) an acidic buffer.
Dependencies are inferred from the claim text.