Dissolution and bioavailability enhancement of glyburide

Abstract

The solubility behavior of drug is one of the most challenging aspects in formulation development, as dissolution and absorption behaviors depend upon this property. The objective of this study was to improve the solubility, dissolution rate, and bioavailability of a poor water-soluble oral hypoglycemic drug glyburide by forming a fast disintegrating tablet using solid dispersion. Attempts were made to improve the solubility of glyburide by fusion method using PEG 20000, vitamin E TPGS or Gelucire 44/14 as carriers at different ratios. The solubility studies were performed in different pH. DSC, X-RD, and FTIR studies were performed to characterize the powder properties. Dissolution-improved solid dispersions were formulated as fast disintegrating tablets. Comparative dissolution studies were conducted for best formulae. Aging was undertaken to determine the performance in dissolution after storage for a three-month period at room temperature. In vivo bioavailability study was carried out for best formulae and pure drug in rabbits. The solubility was increased with elevation in concentration of carrier. All solid dispersions showed enhanced dissolution rate compared to pure glyburide. The solid dispersion of the glyburide with vitamin E TPGS at 1: 0.3 w/w, displayed significant improvement (fourfold) of dissolution in 25 min compared to other carriers. In aging studies, no significant variation was found in their dissolution behavior. DSC and FTIR studies demonstrated that there was no interaction between drug and carrier. XRD showed drug molecules are converted from crystalline to amorphous. The AUC_0-t values for pure drug and solubility improved product were found to be 5766.66 ± 89.12, 24,306.38 ± 121.26, respectively. Data indicated the improved bioavailability of the product with carriers.

Keywords:

• bioavailability
• glyburide
• Vit E TPGS
• Gelucire 44/14
• fast disintegrating
• solid dispersion