Preparation of solid dispersions of glibenclamide for in-vitro dissolution enhancement
The purpose of this study was to prepare solid dispersions (SD) of Glibenclamide (GLB) and evaluate them for in-vitro drug release enhancement. Glibenclamide is a second generation sulfonylurea antidiabetic drug used to control blood glucose in type 2 diabetic patients, but poor-water solubility is responsible for its low oral bioavailability which has severely restricted it in the clinical application for diabetic control. Therefore, to increase the aqueous solubility and thereby, in-vitro dissolution of glibenclamide, solid dispersions were prepared with poloxamer-188in the ratio of 1:1, 1:2; 1:4 & 1:6 by solvent evaporation method in ethanol after conducting preliminary screening for the selection of best carrier and ratio for the development of solid dispersion of glibenclamide . Among the prepared SD formulations, GLB-SD4 (1:6 Drug: Carrier ratio) showed highest enhancement in solubility and in-vitro dissolution rate in phosphate buffer (pH 6.8). In-vitro drug release profiles revealed that the drug release (%) of glibenclamide from GLB-SD4 was achieved 6-fold higher than pure drug after 180 mins. It is worth noting that GLB-SD4 provided the highest solubility and in-vitro dissolution rate compared to rest of the SD formulations, pure glibenclamide, market formulation and physical mixtures of glibenclamide in the same medium (Phosphate Buffer pH 6.8) as per the following manner: GLB-SD4 > GLB-PM4 > GLB-MF>Pure GLB. This may be due to more reduction in particle size at molecular level, enhanced wetting properties and better solubilization of P-188 and use of ethanol. The hydrogen bonding interactions between the drug and carrier in the final solid dispersion formulation (GLB-SD4) was detected by Fourier Transform Infrared (FTIR) spectroscopy. These results demonstrated that the carrier (P-188) proved effective in improving the solubility of a poorly soluble glibenclamide, thereby endorsing the application of solid dispersion technology for the enhancement of solubility and thereby, in-vitro dissolution rate of glibenclamide.
Keywords: Glibenclamide, Solid dispersion, Solubility, In-vitro dissolution, Fourier Transform Infrared.
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