Polymorphism Control And Dissolution Enhancement Of Ritonavir Via Amorphous Solid Dispersion-Based Tablet Formulation

Abstract

Ritonavir, a BCS Class IV HIV protease inhibitor, presents significant formulation challenges due to poor aqueous solubility, low oral bioavailability, and pronounced polymorphic behaviour. The conversion from metastable Form I to the thermodynamically stable but poorly soluble Form II has historically compromised bioavailability. This study aimed to enhance the solubility and dissolution of ritonavir through amorphous solid dispersions (ASDs) prepared by the solvent evaporation technique using hydroxypropyl methylcellulose K100 (HPMC K100) and polyvinylpyrrolidone K30 (PVP K30) as hydrophilic polymeric carriers. Nine ASD formulations (F1–F9) were prepared at varying drug-to-polymer ratios and compressed into tablets using suitable excipients. Precompression parameters including bulk density, tapped density, Carr's index, Hausner ratio, and angle of repose were evaluated. Solid-state characterization was performed using FTIR spectroscopy and differential scanning calorimetry (DSC). FTIR analysis confirmed physicochemical compatibility between ritonavir and the selected polymers, with slight peak shifting suggesting intermolecular hydrogen bonding interactions. DSC thermograms of pure ritonavir showed a sharp endothermic melting peak at 124.80°C, confirming its crystalline nature. This peak was absent in all ASD formulations, confirming successful amorphous conversion. Drug content analysis demonstrated satisfactory uniformity with 98.77% purity. In vitro dissolution studies revealed significantly enhanced drug release from all ASD formulations compared to pure crystalline ritonavir. Formulation F6 exhibited the highest cumulative drug release of approximately 104% at 30 minutes. The enhanced dissolution was attributed to amorphous conversion, improved wettability, increased surface area, and effective polymer-drug interactions. The study conclusively demonstrates that solvent evaporation-based ASD technology is an effective an0d promising strategy for improving the dissolution and oral delivery of ritonavir.