INCLUSION COMPLEXATION OF GLIBENCLAMIDE WITH 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN IN SOLUTION AND IN SOLID-STATE

Phase solubility diagrams have been used to investigate complexation between 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and glibenclamide (GM) in aqueous medium. More stable GM-HPBCD complexes were formed in alkaline medium (in which the drug is in ionized form) than in acid medium (in which the drug is in non-ionized form). The formation of solid GM-HPBCD inclusion complexes has been evaluated by using kneading, spray-drying and freeze-drying methods. Characterization of the resulting mixtures by X-ray diffraction, infrared spectroscopy and differential scanning calorimetry indicated that inclusion complexes can be obtained by spray drying and freeze drying but not by kneading. According to the phase solubility results, drug solubility in alkaline medium was greatly improved by inclusion with HPBCD, whereas in acid medium inclusion with HPBCD had no appreciable effect. Cyclodextrin complexation of ionized drug molecules in alkaline medium resulted in greater total solubilization, i.e., solubilization of the drug due to both cyclodextrin complexation and ionization.