Polyalkoxylated alcohols as excipients for pharmaceutical compositions

摘要

The present invention relates to the use of polyalkoxylated alcohols of the formula R—O-(AO)—H, wherein R is a substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, aralkyl or heterocyclic group having 7 to 25 carbon atoms, (AO) is a polyoxyalkylene moiety of the composition (BO)m(EO)n(DO)r with random or blockwise arrangement of the constituting oxyalkylene units, wherein m, n and r represent the average number of oxybutylene (BO) units, oxyethylene (EO) units and oxyalkylene units derived from at least one epoxide selected from styrene oxide and alkylene oxides having from 5 to 10 carbon atoms (DO) per molecule of the polyalkoxylated alcohol, respectively, m being a number greater than or equal to 1, n being a number greater than or equal to 1 and r being a number in the range from 0 to 50 under the proviso that (m+n+r) is less than or equal to 200 and the ratio n/(m+r) is in the range of 1 to 20, as excipients in pharmaceutical compositions. Said polyalkoxylated alcohols enable very effective solubilization of poorly soluble active pharmaceutical ingredients in aqueous media. Solid or semi-solid pharmaceutical compositions comprising one or more such polyalkoxylated alcohol combined with at least one active pharmaceutical ingredient are further long term stable under typical storage conditions and can be readily provided in various dosage forms such as tablets and filled capsules.

主权项

1. Solid or semi-solid pharmaceutical composition comprising
a) at least one active pharmaceutical ingredient, and b) at least one polyalkoxylated alcohol, wherein said at least one active pharmaceutical ingredient alone has a solubility in distilled water of pH 7.0 of 10 mg/L or less at a temperature of 22° C. and an atmospheric pressure of 1 atm, and wherein said at least one polyalkoxylated alcohol is a polyalkoxylated alcohol of the formula
R—O-(AO)—Hwherein R is an unsubstituted alkyl, alkenyl, alkynyl, aryl or aralkyl group, the group R having 7 to 25 carbon atoms, (AO) is a polyoxyalkylene moiety of the composition (BO)m(EO)n with blockwise arrangement of the constituting oxyalkylene units, wherein m and n represent the average number of oxybutylene (BO) units and oxyethylene (EO) units, respectively, m being a number greater than or equal to 1 and n being a number greater than or equal to 1 under the proviso that (m+n) is less than or equal to 200 and the ratio n/(m) is in the range of 1 to 20.