Effects of 2-hydroxypropyl-beta-cyclodextrin on the solubility of metronidazole in aqueous solution

Abstract

The purpose of this present study was to explore the effects of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) on the solubility and stability of metronidazole in aqueous solution. From the phase solubility study, the aqueous solubility of metronidazole increased linearly as function of HPBCD concentration. The phase solubility diagram of metronidazole can be classified as type A[subscript L] and the stability constant was estimated as 11.24 M[superscript -1]. Freeze-drying method was used to prepare solid complex of metronidazole:HPBCD (1:2 molar ratio). The complexes obtained were characterized in the solid phase by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry, and in the liquid phase by proton nuclear magnetic resonance spectroscopy. The results obtained from proton nuclear magnetic resonance spectroscopy indicated that metronidazole was shown to form inclusion complex with HPBCD. The studies of effects of temperature, pH and light on the stability of complex showed that the kinetic of metronidazole:HPBCD degradation followed first-order except for the photochemical degradation which followed zero-order. HPBCD appears to retard the degradation of metronidazole by forming inclusion complex except at pH 3.1. On the other hand, HPBCD has a tendency to accelerate the photodecomposition of metronidazole.