ENHANCING ORAL BIOAVAILABILITY OF CARVEDILOL USING SOLID DISPERSION TECHNIQUE

Objective: Carvedilol (CRV) is a beta blocker drug that is basically used for the treatment of hypertension, heart failure and arrhythmias. The objective of this study is to increase the oral bioavailability of CRV by using solid dispersions to enhance its solubility and dissolution rate.Methods: Various preparations of CRV-solid dispersions (SDs) and physical mixtures (PMs) were prepared using different carriers; polyethylene glycol (PEG) 4000, polyvinyl pyrrolidone (PVP) K30 and tartaric acid. Effect of type and concentrations of carriers on solubility and dissolution of CRV were studied. Selected CRV-SDs and PMs that showed the best solubility and dissolution were exposed for further investigations e. g. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD). In addition, the oral antihypertensive activity of the optimized formula compared to pure CRV was evaluated in induced hypertensive adult albino male rats.Results: All carriers enhanced the dissolution rate of CRV. Tartaric acid had the most persuasive effect on the rate and the extent of dissolution of CRV, followed by PEG4000 and PVP. FTIR, DSC and XRD diffraction revealed an interaction between CRV and tartaric acid with the possibility of a polymorphic change in CRV. The optimized formula CRV-tartaric acid (SD 1:0.3) causes a marked increase in the antihypertensive activity compared to pure CRV.Conclusion: Tartaric acid is a promising and efficient carrier for improving the solubility, dissolution and oral bioavailability of CRV.Keywords: Carvedilol, Solid dispersion, Physical mixture, Hypertension, Oral bioavailabilit