Enhanced Solubility and Dissolution of Drug-drug Cocrystals of Lopinavir-Ritonavir

Abstract:

Introduction: Drug-drug cocrystals of Lopinavir and Ritonavir were designed and characterized. In view of literature, Ritonavir increases the oral bioavailability of Lopinavir in low dosage. Aim: The present research aimed to improve the solubility, dissolution, and oral bioavailability of Lopinavir through a cocrystallization approach using Ritonavir as a coformer. Materials and Methods: Cocrystallization was carried out using wet grinding and solvent evaporation methods. Prepared Cocrystals were examined and evaluated using characterization methods such as DSC, PXRD, FTIR, Polarized light microscopy, % Drug content, FE-SEM, Micromeritics properties, Solubility, Dissolution, and Stability studies as per ICH guidelines. Results: Developed cocrystals were showed superior solubility and dissolution as compared to pure drug. After 48 hr, aqueous solubility of Lopinavir and Ritonavir co-amorphous formulation (LRCWG) was increased 3.7-fold in the wet grinding method, while Lopinavir and Ritonavir Cocrystals Prepared by Solvent Evaporation Method (LRCSE) indicated 5.9-fold increase compared to pure drug. The co-amorphous formulation was developed using wet grinding showed 86% drug release at 60 min, and cocrystals synthesized through solvent evaporation method showed 94% of drug release. Conclusion: Cocrystals produced using solvent evaporation approach were stable and showed excellent physico-chemical characteristics. The study concluded that the cocrystallization approach would prove to be a successful method to improve physico-chemical and mechanical properties.

Keywords: Lopinavir, Ritonavir, Multi-Drug Cocrystals, Solubility, Dissolution.