Abstract

DRUG COMBINATION APPROACH FOR SOLUBILITY ENHANCEMENT OF ANTIDIABETIC DRUGS

Neelam Seedher* and Mamta Kanojia

ABSTRACT

Poor aqueous solubility is often a major factor that limits the bioavailability and development of oral hypoglycemic agents. Since combination therapy is common in type II diabetes, drug combination approach has been used for the first time to enhance the solubility of seven poorly-soluble antidiabetic drugs. Pure drug samples/drug mixtures were stirred with the appropriate solvent for 24 hours at 250C and the supernatant obtained by centrifugation was filtered through 0.45μm filter. Ultraviolet absorption spectrophotometric technique was used for drug analysis. A very large increase in the aqueous solubility was observed. In general, the combined effect of combination drug and buffer produced much larger solubility enhancement. The solubility of glitazones, however, decreased in buffer medium. In the ternary systems, the effect was especially significant in combinations involving rosiglitazone maleate, an enormous increase in the solubility of most sulfonylureas and rosiglitazone maleate was observed. A 631 and 1200 times increase in the solubility of practically insoluble drugs glibenclamide and glimepiride is particularly noticeable. Thus drug combination approach can be used as an effective technique to enhance the solubility of poorly soluble antidiabetic drugs. The results can have far reaching implications in the development of formulations for combination therapy and understanding the pharmacological response of drugs in multidrug therapy.

Keywords: drug combination approach solubility antidiabetic drugs.