چکیده (انگلیسی):

The purpose of this research was to improve the solubility and therefore dissolution and bioavailability of triamterene, a poorly water soluble diuretic, by complexation with β-cyclodextrin. Triamterene has been reported to show low bioavailability after oral administration, with wide intersub-ject variation. This study presents the formulation of solid dispersions of triamterene with β-cyclodextrin—by cogrind-ing, kneading, and coevaporation, using low pH condi-tions—and their characterization, evaluation of improve-ment in dissolution profiles, and in vivo advantage. Phase solubility studies indicated complex with possible stoichiometry of 1:1 and a stability constant of 167.67M-1. The solid dispersions were characterized by Fourier trans-form infrared spectroscopy, nuclear magnetic resonance, x-ray diffraction, and differential scanning calorimetry studies. The characterization studies confirmed inclusion of the phenyl ring of triamterene within the nonpolar cavity of β-cyclodextrin in the coevaporate. Remarkable improvement in in vitro drug release profiles in 0.1N HCl and pH 6.8 phosphate buffer was observed with all dispersions, espe-cially the coevaporate. The coevaporate, when administered orally in rats, also exhibited improved in vivo activity, as measured by net sodium ion excretion, as compared with triamterene powder. Thus, coevaporation of the drug and β-cyclodextrin from acidified alcohol provide the optimum condition for inclusion complexation to give a binary system with remarkable improvement in in vitro drug release profile and in vivo performance.