Development and Evaluation of Ritonavir Co-Crystal for Improved Solubility and Dissolution Profile
DOI:
https://doi.org/10.22270/ajprd.v14i5.1868Abstract
Ritonavir is a highly lipophilic antiretroviral drug whose poor aqueous solubility can limit its dissolution and oral drug delivery performance. The present study was designed to develop ritonavir–tartaric acid pharmaceutical cocrystals as a solid-state approach for improving the aqueous solubility and dissolution behavior of ritonavir. Tartaric acid was selected as a hydrophilic coformer, and cocrystals were prepared using co-grinding, solvent evaporation, and liquid-assisted grinding techniques at ritonavir:tartaric acid molar ratios of 1:1, 1:2, and 1:3. The prepared cocrystals were evaluated for saturation solubility, drug content, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The optimized cocrystal system was subsequently incorporated into tablet formulations and evaluated for pre-compression and post-compression characteristics and in-vitro drug release. The saturation solubility study demonstrated a concentration-dependent improvement in ritonavir solubility. Among the tartaric acid cocrystals, RCTS3 prepared by solvent evaporation at a 1:3 molar ratio exhibited the highest solubility of 6.12 mg/mL, compared with 3.02 mg/mL for RCTG1 prepared by co-grinding at a 1:1 ratio. The drug content of the prepared cocrystals ranged from 94.86% to 98.65%, indicating satisfactory drug incorporation. FTIR and thermal studies demonstrated changes in the molecular environment of ritonavir after cocrystallization, supporting intermolecular interactions between ritonavir and tartaric acid. The prepared tablet blends exhibited acceptable flow and compression characteristics. Among the ritonavir–tartaric acid tablet formulations, RCTG3T exhibited the highest cumulative drug release of 99.70% at 12 h, followed by RCTG2T (97.70%) and RCTG1T (96.60%). The study demonstrated that cocrystallization with tartaric acid is a promising strategy for enhancing the solubility and dissolution performance of ritonavir, while maintaining satisfactory pharmaceutical processing characteristics.
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