Nanocrystals as a Novel Pharmaceutical Approach for Bioavailability Enhancement: A Comprehensive Review

The majority of new drug molecules discovered through high-throughput screening possess poor aqueous solubility, resulting in low oral bioavailability and limited clinical success. Nearly 40–70% of small-molecule drugs fall into Biopharmaceutics Classification System (BCS) Class II or IV, where solubility and dissolution are the rate-limiting steps in absorption. Nanocrystal technology has emerged as a simple yet powerful strategy to address these issues by reducing drug particles to the nanometer scale, thereby increasing surface area, dissolution velocity, and apparent saturation solubility. Unlike polymeric nanoparticles or lipid carriers, nanocrystals consist almost entirely of the pure active pharmaceutical ingredient stabilized by surfactants or polymers, offering high drug loading and improved performance. This review provides a comprehensive overview of nanocrystals as a drug delivery approach, discussing their theoretical basis, preparation methods, stabilizers, characterization techniques, pharmaceutical applications, marketed products, regulatory aspects, stability concerns, and future perspectives. Tables and figures are included to aid clarity.