Inclusion Complexation of Antihypertensive Drug for Solubility Enhancement to Increase Its Bioavailability

Abstract

Carvedilol is a β- adrenergic receptor blocker, and it has the ability to decrease the heart rate, myocardial contractility and myocardial oxygen demand. It competitively blocks β-1, β-2 and α-1 receptors. it also lacks sympathomimetic activity and has vasodilating properties that are extended primarily through α-1 blockade. The poor aqueous solubility of carvedilol leads to poor bioavailability and poor dissolution rate in the biological fluid. Therefore, it can be overcome by inclusion complexation using β- cyclodextrin. The inclusion complexes of carvedilol were made using different concentrations of β- cyclodextrin and behaviour of β-cyclodextrin was studied towards the carvedilol in order to develop a new oral dosage form having enhanced dissolution rate and bioavailability. On studying the phase diagram of carvedilol it showed AL type phase solubility. Inclusion complexes with β-cyclodextrin and its physical mixture with different ratios were studied for dissolution study and their characterisation was confirmed by DSC, FTIR and SEM analysis. Inclusion complexes of carvedilol were successfully formed and showed more drug release profile as compared to their physical mixtures. The significant improvement in the rate of release of β-CD complex formulation can help in appreciable reduction in the lag time of the drug absorption, characterised by high tmax values (120 minutes), thereby can improve the rate of bioavailability and onset of its therapeutic effects.