Micellar Solubilization of Some Poorly Soluble Antidiabetic Drugs: A Technical Note

Abstract

Poor aqueous solubility is usually a major obstacle in the development of therapeutic agents. Some of the approaches commonly used to enhance the solubility of poorly soluble drugs include use of co-solvents (1–2), selection of salt form (3–4), increase of specific surface area by reduction of particle size (5), complex formation with excipients such as hydrophilic polymers and cyclodextrins (6–8), change of crystal form (polymorphism/amorphism) (9) and preparation of solid dispersions (10–11). Micellar solubilization is a widely used alternative for the dissolution of poorly soluble drugs (12–14). Depending upon the drug hydrophobicity, it can be solubilized in the inner core of the micelle, on the surface of the micelle or at an intermediate location in the palisade layer. Solubilization of drugs by surfactant systems has been reviewed and discussed by many investigators (15–17). The antidiabetic drugs used in the present work belong to class II (poor solubility and high permeability) of the biopharmaceutical classification system (BCS). Improvement in the solubility of glyburide by solid dispersion technique has been reported (18). Ammar et al. (19) have shown that the association of water soluble polymers with glimepiride–cyclodextrin systems leads to great enhancement in the dissolution rate of the drug. Complexation with cyclodextrin has been reported to increase the solubility of gliclazide (20–21). Surfactants have also been used to enhance the solubility of antidiabetic drugs (22–23). Alkhamis et al. (22) have studied the solubilization efficiency and locus of solubilization of gliclazide for various surfactants. A hydroalcoholic surfactant solution with a relatively low alcohol and Tween-80 content buffered at pH 7.4 has been used as dissolution medium for glyburide (23). However, detailed studies on surfactant solubilization of a wide range of antidiabetic drugs have not been reported. In addition to improving solubility and bioavailability of drugs, the use of micelles as drug carriers also presents other advantages such as reduced toxicity, enhanced permeability and longer residence time in the system (16). In the present paper an attempt has been made to enhance the solubility of seven antidiabetic drugs, gliclazide, glyburide, glimepiride, glipizide, repaglinide, pioglitazone and rosiglitazone using cationic, anionic and non-ionic surfactants and their mixtures.