Improvement of solubility and dissolution rate of Repaglinide by Liquisolid Compact technique: QbD approach

Abstract

The bioavailability and therapeutic efficacy of several active molecules is limited due to poor solubility. Repaglinide is used to lower plasma glucose levels, especially in type II diabetes mellitus, and its activity is low due to extensive first-pass metabolism and poor solubility. The current research focused on improving the solubility and thus accelerating the dissolution rate of repaglinide for its antidiabetic effect. Liquisolid Compact technique was used for potent therapeutic molecules, which improved the solubility, dissolution rate and thus bioavailability using non-volatile solvents. Repaglinide was readily soluble in PEG 200 at 241 mg/ml. Incorporation of PEG 200 resulted in conversion of solid drug to liquid drug and conversion back to powder form was achieved by incorporation of carrier and coating agents. The compatibility of repaglinide with all excipients was tested by FTIR and the compatibility with excipients was confirmed. Before compression, all powder mixtures were tested for their flow properties such as Carr index and angle of repose, etc. Optimization was performed using Design of Expert, applying 32 Box-Behnken designs consisting of 3 independent parameters (DCP, Aerosil 200 and CP) and reliable parameters (decay and dissolution time). The optimized batch F1 showed good flow properties, low disintegration time and higher dissolution rate of 99.56% within 30 minutes. In addition, the optimized batch successfully passed the stability test.

Keywords

• Repaglinide
• Liquisolid technique
• solubility enhancement
• Box Behnken design

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