Formulation of Co-crystals of Lopinavir using Co-former to Enhance Solubility and Bioavailability
Abstract
The poor aqueous solubility and limited oral bioavailability of many antiviral drugs, particularly lopinavir, present major challenges to effective oral drug delivery. Lopinavir exhibits low solubility, poor intestinal permeability, and variable absorption, resulting in reduced therapeutic efficacy. The present study aimed to develop and evaluate pharmaceutical cocrystals of lopinavir using pharmaceutically acceptable coformers to enhance its physicochemical and biopharmaceutical properties without altering its pharmacological activity. Cocrystals were prepared using crystal engineering techniques, including solvent evaporation, slurry conversion, and solvent-assisted grinding. The prepared formulations were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM), to confirm cocrystal formation and investigate structural modifications. Solubility, dissolution, and stability studies were conducted to compare the optimized cocrystals with pure lopinavir. The results demonstrated a marked improvement in aqueous solubility and dissolution rate, attributed to the formation of a modified crystal lattice and intermolecular hydrogen-bonding interactions between lopinavir and the selected coformer. The optimized cocrystals also exhibited satisfactory physicochemical stability while maintaining the therapeutic integrity of the drug. These findings suggest that pharmaceutical cocrystal engineering is a promising, scalable, and regulatory-acceptable approach for enhancing the oral bioavailability and therapeutic performance of poorly soluble antiviral drugs such as lopinavir. Improved dissolution characteristics may contribute to reduced dose variability, enhanced patient compliance, and better clinical outcomes.
Keywords: Pharmaceutical cocrystals; Antiviral drugs; Solubility enhancement; Bioavailability; Coformers; Dissolution rate; Drug delivery; Crystal lattice modification
Keywords:
Pharmaceutical cocrystals, Antiviral drugs, Solubility enhancement, Bioavailability, Coformers, Dissolution rate, Drug delivery, Crystal lattice modificationDOI
https://doi.org/10.22270/jddt.v16i10.8040References
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