Improvement of gliquidone hypoglycaemic effect in rats by cyclodextrin formulations

Improvement of gliquidone hypoglycaemic effect in rats by cyclodextrin formulations
September 2004
A. Miro, F. Quaglia, U. Sorrentino, M. I. La Rotonda, R. D?Emmanuele Di Villa Bianca and R. Sorrentino
European Journal of Pharmaceutical Sciences Volume 23, Issue 1 , September 2004, Pages 57-64
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Abstract
This study was carried out with the aim to optimize the pharmacological profile of gliquidone (GLI)?a poorly bioavailable hypoglycaemic agent sparingly soluble in water- through complexation with cyclodextrins. In order to increase the apparent solubility of GLI, two cyclodextrins, namely small beta, Greek-cyclodextrin (small beta, GreekCD) and hydroxypropyl-small beta, Greek-cyclodextrin (HPsmall beta, GreekCD), were tested. The effect of cyclodextrin addition on the aqueous solubility of GLI was evaluated by the phase solubility method at different pH values. The amount of GLI in solution increased upon CD addition according to A type plots. The aqueous solubility of GLI was enhanced more at higher pH values and using HPsmall beta, GreekCD. On the basis of its performance, HPsmall beta, GreekCD was selected as host to prepare GLI oral formulations. GLI/HPsmall beta, GreekCD solid systems were prepared at 1:2 molar ratio by co-grinding, spray-drying and freeze-drying and characterized by DSC, FTIR and X-ray powder diffractometry. Powders were amorphous and showed an improved dissolution rate in comparison with GLI. GLI/HPsmall beta, GreekCD co-ground and freeze-dried products were the most interesting systems, since they dissolved 62 and 94% of total drug after 15 min, respectively. The hypoglycaemic effect of the most rapidly dissolving binary systems was evaluated after oral administration in fasted rats by measuring plasma glucose level in the time interval 0.5?36 h and compared to free GLI. Our findings indicate that cyclodextrin-containing formulations not only provide an onset of hypoglycaemic effect faster than GLI, but also enhance significantly the pharmacological effect due to improved biopharmaceutics. The association GLI/HPsmall beta, GreekCD allows a reduction of the oral dose and is expected to provide a better control over drugn side effects, contributing to improve safety and efficacy of GLI.