Solubility Enhancement of Poorly Water-Soluble Drug Ritonavir using Polyvinylpyrrolidone and Chitosan-based Platform Technique

Abstract

The antiviral medication ritonavir (RTV) belongs to the biopharmaceutics classification system (BCS) class II drug category and is known for its high permeability and poor solubility. Therefore, the prime objective of this research was to increase the rate of dissolution and improve the solubility of RTV using a polymer system. Solid dispersions consisting of binary polymer components i.e., chitosan (CH) and polyvinylpyrrolidone (PVP) were prepared using microwave microwave-assisted physical mixing technique and optimization of solid dispersion was performed with 32 factorial designs. Dispersions were analyzed for their physicochemical characteristics by the use of X-ray diffraction (XRD), differential scanning calorimetry (DSC), and fourier transform infrared spectroscopy (FTIR). The polymeric dispersions prepared were evaluated for the release of RTV throughout 1 h in 0.1N sodium chloride in a USP class II dissolving device. The phase solubility study demonstrated a considerable improvement in the saturation solubility of RTV when CH and PVP K30 were present either individually or in combination. Virtual interaction studies between the drug and polymers revealed physical interactions driven by van der Waals and hydrophobic forces between RTV and excipients. Carbonyl, amine, and hydroxyl groups, among others, were probably present in both RTV and CH, which allowed for these interactions to take place. There was no discernible interaction between the RTV and the polymers included in the FTIR research. The dispersion strategies have improved the dissolving rate, according to the in-vitro drug release investigation. A formulation including a polymeric dispersion of the optimal concentration of PVP and chitosan may efficiently boost the release of RTV, according to the in-vitro release profile.