Dissolution method evaluation for carvedilol tablets

Abstract

Carvedilol is an antihypertensive agent with blocking non-selective (selectivity for β1 and β2 adrenoceptors is moderate) with vasodilating properties conferred on the α-receptor blockade. The molecular structure has one chiral center, so the drug exists as two enantiomers. Furthermore, it presents different polymorphs depending on the synthetic route that is used to obtain the drug. Carvedilol is a weak base, practically insoluble in water, acidic solutions, and gastric and intestinal fluids, and is classified as Class II (Biopharmaceutical Classification System). It presents different solubilities in accordance with the pH of the solvent. In a previous report, it was demonstrated that batches provided by different manufacturers could have different physicochemical properties. The objective of the present study is to evaluate these properties in the formulation of the final tablets and evaluate the best dissolution method. Different media were used to evaluate the impact of raw material characteristics on in vitro release of drug from tablets containing 12.5 mg carvedilol. Pilot batches were obtained by direct compression and wet granulation. Dissolution profiles were compared with a reference drug. Formulations evaluated by wet granulation using carvedilol with a specific particle size (d10 ~ 10 μm and d90 ~ 95 μm) had similar dissolution profiles to the reference product according to United States Pharmacopeia test 2 and fasted-state simulated intestinal fluid (FaSSIF). The results showed the composition of dissolution medium has a direct impact on the dissolution profile of carvedilol.