Enhanced solubility and bioavailability of ranolazine by solid dispersion method in vitro and in vivo evaluation

Abstract

Objective: This study aims to formulate solid dispersions incorporating ranolazine to enhance its aqueous solubility. Methodology: The poor aqueous solubility and permeability of BCS class II drug hamper their bioavailability when orally or topically administered. The present research study focused on formulating amorphous solid dispersions of ranolazine. The hydrophilic polymeric carriers like, HPMC, PEG 6000 and PVPK 30K, Soluplus were used in different ratio. Solid dispersions were prepared by employing modified solvent evaporation method. The prepared physical mixtures and solid dispersions were physico-chemically characterized using fourier transform infrared spectroscopy, scanning electron microscopy, powder x-ray diffractometry, drug content estimation by UV-spectrophotometric method. Result: Functional evaluation of ranolazine solid dispersions was carried out by solubility analysis, in-vitro dissolution studies and pharmacokinetics study. According to solubility studies, Soluplus showed the highest solubility profile among the polymers tested. An optimized ranolazine containing solid dispersions formulation composed of Soluplus at 1:2.5 ratio had 10 fold (41.21 ± 0.35μg/mL) higher solubility and dissolution over that of pure ranolazine (~ 3.92 ± 0.06μg/mL) and physical mixture (~ 4.51 ± 0.32μg/mL). In-vitro dissolution studies revealed that there was increase in solubility of drug and enhanced dissolution rate in solid dispersions compared to physical mixtures respectively.