Self-assembly supramolecular ternary co-crystal systems containing Glibenclamide: physicochemical and Pharmacodynamic studies

Abstract

The bioavailability of the drug is affected to a great extent by drug solubility. Most of the available and developed drugs are classified as poorly water-soluble drugs. The aim of this work is to formulate a ternary co-crystal matrix of Glibenclamide (GB) with the aid of Nicotinic acid (NA) as coformer and Brij-35 as surfactant, to enhance the solubility of the drug. Based on a statistical design at a level of 3², nine different matrices were prepared and characterized for their flow properties and in vitro dissolution rate. Although the dissolution rate of all formulations was better than that of pure drug, the flowability of the powder is very important. The optimized formula, which is composed of 2.81 NA and 0.5 Brij-25, has good flowability in terms of Carr's index of 18.9 % and enhancement in the dissolution rate by 1.4-fold. In addition, the XRPD for the optimized formula shows a new peak that does not appear in the physical mixture. This may indicate the formation of new compounds that have better dissolution rates. The pharmacodynamics of the optimized matrix was tested against the pure drug, and it showed a significant reduction in fasting blood glucose level (P = 0.01).