Inclusion parameters of pioglitazone hydrochloride and glipizide with β-cyclodextrin and its methyl derivative: calorimetric and

Abstract

Solution calorimetry, a direct method to determine the thermodynamic parameters was used to investigate the inclusion phenomenon (stability constant, K; complexation enthalpy, ΔHo) of two poorly soluble oral hypoglycemic agents, pioglitazone hydrochloride  (pioglitazone HCl) and glipizide with ß- cyclodextrin (ß-CD) and its methyl derivative (methyl-ß-CD). The inclusion complexes prepared by kneading were characterized in the solid state by differential scanning calorimetry and X-ray powder diffraction. The host-guest geometry and stoichiometry for the complexes indicated by proton NMR studies was confirmed by solution calorimetry. In case of pioglitazone HCl, two types of 1:1 complexes co-existing in solution have been revealed as pyridine ring as well as thiazoledione ring can be included in the cavity of cyclodextrin. The value of K1 and K2 determined using two class binding model utilizing non-linear least square regression was found to be 1940 M-1 and 1478 M-1 at pH 8 for complex with ß-CD. Glipizide, a bigger molecule showed 1:2 complex with ß-CD with a stability constant of 1880 M-1 at pH 8 with ß-CD. The magnitude of equilibrium constants decreased at pH 4 which is attributed to the presence of ionized species for both the drug molecules at lower pH. The inclusion of the drugs in the cyclodextrin cavity is an exothermic process accompanied by small negative value of ΔGo and positive value of ΔSo. The magnitude of equilibrium constant increased with the use of methyl-ß-CD for both drugs indicating their better complexing ability. This supports the enhanced solubility and dissolution rates observed with methyl-ß-CD.

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Keywords: Pioglitazone, glipizide, encapsulation, solubility, calorimetry, equilibrium constant.