Preparation and Characterization of Drug Nanocrystals to Enhance Solubility of Poorly Water-Soluble Drugs

Abstract

This work investigates the preparation and characterization of drug nanocrystals as a strategy to enhance the solubility and dissolution behavior of poorly water-soluble drugs, particularly those classified under Biopharmaceutics Classification System (BCS) Class II and IV. Poor aqueous solubility remains a critical challenge in pharmaceutical development, often leading to limited bioavailability and suboptimal therapeutic performance. In this study, drug nanocrystals were prepared using both top-down and bottom-up approaches, specifically high-pressure homogenization and antisolvent precipitation. Stabilization was achieved using suitable surfactants and polymers to prevent aggregation and ensure nanoscale stability. Comprehensive physicochemical characterization was performed using dynamic light scattering (DLS) for particle size and polydispersity index, zeta potential analysis for stability assessment, scanning electron microscopy (SEM) for morphology, differential scanning calorimetry (DSC) for thermal behavior, and X-ray diffraction (XRD) for crystallinity evaluation. In addition, in vitro dissolution studies were conducted to assess drug release performance. The results showed a significant reduction in particle size to the range of 100–300 nm with a narrow size distribution and sufficient zeta potential, indicating good colloidal stability. Morphological analysis confirmed the formation of uniform and nanosized particles, while thermal and XRD studies indicated retention of crystalline structure with slight amorphization. Notably, nanocrystal formulations exhibited a 2–3 fold enhancement in dissolution rate and improved saturation solubility compared to the coarse drug. Overall, this study demonstrates that nanocrystal technology is a scalable, carrier-free, and effective approach for improving the solubility, dissolution, and potential bioavailability of poorly water-soluble drugs.