Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes

BCS class II drugs exhibit low aqueous solubility and high permeability. Such drugs often have an incomplete or erratic absorption profile. This study aimed to predict the effects of β-cyclodextrin (βCD) and different hydrophilic polymers (poloxamer 188 (PXM-188), polyvinyl pyrrolidone (PVP) and soluplus (SOLO)) on the saturated solubility and dissolution profile of hydrophobic model drug rivaroxaban (RIV). Binary inclusion complex with βCD were prepared by kneading and solvent evaporation method, at drug to cyclodextrin weight molar ratios of 1:1, 1:2, and 1:4. Saturated solubility of the hydrophobic model moiety was evaluated with βCD to explore the increment in saturated solubility. Dissolution test was carried out to assess the drug release from the produced binary inclusion complex in the aqueous medium. Solid state analysis was performed using Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques. When compared to pure drug, the binary complex (Drug: βCD at molar ratio of 1:2 w/w) demonstrated the best performance in terms of enhanced solubility and drug release. Furthermore, ternary inclusion complex was prepared with hydrophilic polymers SOLO, PVP K-30 and PXM-188 at 0.5%,1%,2.5%,5% and 10% w/w to optimized binary formulation RIV:βCD (1:2) prepared by kneading (KN) and solvent evaporation (S.E) method. The findings demonstrated that among ternary formulations (1:2 Drug: βCD: SOLO 10% S.E) manifested greatest improvement in saturated solubility and dissolution rate. Results of solubility enhancement and improvement in dissolution profile of model drug by ternary inclusion complexation were also supported by FTIR, DSC, XRD, and SEM analysis. So, it can be concluded that the ternary inclusion systems were more effective compared to the binary combinations in improving solubility as well as dissolution of hydrophobic model drug rivaroxaban.