Improvement of Oral Bioavailability of Carvedilol by Liquisolid Compact: Optimization and Pharmacokinetic Study

Abstract

Low aqueous solubility is one of the major reasons for the poor clinical efficacy of carvedilol in oral therapy. The aim of the present investigation was to evaluate the potential of liquisolid compact technique to enhance the dissolution rates of carvedilol and thereby the bioavailability. Liquisolid compactswere prepared using polyethylene glycol 400, Neusilin US2 and Aerosil 200. Experimental design and optimizationwas carried out by applying a 32 factorial design (batches D1-D9) to examine the effects of independent variables (amount of load factor and the excipient ratio) on dependent variables (angle of repose and%drug release).Differential scanning calorimetry and X-ray diffraction studies suggested transformation of carvedilol to amorphous in D6, a key factor responsible for dissolution rate improvement. This effect was evidenced in the dissolution data of D6 (>95% drug dissolved in 30 min) where the drug release kinetics followed Weibull model. It was observed that the amount of load factor influenced angle of repose and excipient ratio affected drug dissolution of liquisolid compacts. Pharmacokinetic profile of D6 was prominent, demonstrating greater carvedilol absorption than the control in rats. The observed increase in systemic bioavailability of carvedilol AUC0-∞ (p < 0.005) by liquisolid compact is likely due to the improvement in drug solubility. The data observed in the current study demonstrated that the liquisolid compact technique could be a promising strategy to enhance the bioavailability of carvedilol and could be used in oral therapy.