Improved Dissolution and Bioavailability of Eprosartan Mesylate Formulated as Solid Dispersions using Conventional Methods

Abstract

Background: Eprosartan mesylate (EM) is a poorly aqueous soluble drug belonging to BCS-class II suffers from low bioavailability (13%). The present study involves an effort for improving dissolution and thus the bioavailability of EM using solid dispersion approach. Methods: Solid dispersion (SD) was prepared by melting, solvent evaporation and kneading method using different ratios of drug and polymers (PEG-4000, Eudragit E-100, PVP K-30, Poloxamer-407, and Eudragit L-100). Phase solubility study revealed highest solubility in PVP K-30 at 1:2 ratios. The solid state characterizations of selected solid dispersion formulation (SD-15) were performed by infrared spectroscopy, differential scanning calorimeter, X-ray diffraction study and scanning electron microscopy. In vitro dissolution was carried out in phosphate buffer (pH 7.4) at 50 rpm in 900 ml of volume. The in vivo pharmacokinetic study of selected formulation (SD-15) was carried out in male Wistar rats using non-compartment analysis by linear trapezoidal method after a single oral dose of 10 mg/kg of EM. Results: The solid state characterization revealed no such drug-polymer interactions and rapid transformation of crystalline drug in an amorphous state, which amplifies the aqueous solubility and hence the dissolution rate. The in vitro dissolution study of the dispersions prepared by PVP K-30 (1:2) was found to be 95.5% after 1 hr. In vivo pharmacokinetic study in Wistar rats showed significant improvement in oral bioavailability of EM in SD-15 with the 2.4 fold increments than the pure drug. Conclusion: The solid dispersion prepared using PVP K-30 by kneading method showed improved dissolution and bioavailability. Therefore, solid dispersion formulation can be sorted as a promising approach for improving the dissolution and bioavailability of Eprosartan mesylate.

The preparation and physicochemical characterization of eprosartan mesylate-laden polymeric ternary solid dispersions for enhanced solubility and dissolution rate of the drug

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Effect of molecular interaction on the antiplasmodial efficacy of lumefantrine in amorphous polymethacrylate-urea solid solution

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