CELLULOSE DERIVATIVES FOR INHIBITING CRYSTALLIZATION OF POORLY WATER-SOLUBLE DRUGS

摘要

The present invention relates to the fields of chemistry and pharmaceuticals. Embodiments of the invention provide cellulose esters useful for inhibiting solution crystallization of drugs. Specific polymers of the invention include cellulose esters of formula (I) : wherein n of the omega-carboxyalkanoyl group, Formula (II), is 3, 4, 6, or 8 to provide a omega-carboxyalkanoyl group chosen from succinoyl, glutaroyl, adipoyl, sebacyl, and suberyl groups; and wherein R is chosen from : a hydrogen atom; and an alkanoyl group chosen from acetyl, propionyl, butyryl, valeroyl, hexanoyl, nonanoyl, decanoyl, lauroyl, palmitoyl, and stearoyl groups; wherein there is a total degree of substitution of the alkanoyl group and the omega-carboxyalkanoyl group of at least 2.0; and wherein the polymer comprises m repeating units where n = 1 to 1,000,000, or 10 to 100,000, or 100 to 1,000, such as 1 to 6,000. Embodiments further include compositions comprising cellulose esters and poorly water-soluble drugs, which compositions exhibit greater solubility and stability in solution as compared to the drugs alone. Drugs that can be used in combination with such polymers include but are not limited to ritonavir, efavirenz, etravirine, celecoxib, clarithromycin, curcumin, ellagic acid, quercetin, naringenin, and resveratrol. Methods for making and using the compounds and compositions are also included within the scope of the invention.