Nanocrystals: For Solubility Enhancement of Hydrophobic Drug

The oral administration of numerous therapeutic compounds is frequently hindered by their limited solubility in water, which results in poor and inconsistent bioavailability. Drugs belonging to Biopharmaceutical Classification System (BCS) Class II demonstrate good membrane permeability but inadequate solubility, making dissolution the key step controlling absorption. To address this limitation, several formulation strategies have been explored, among which nanocrystal technology has gained considerable attention as an efficient and straightforward approach for improving dissolution behavior and solubility. Drug nanocrystals, consisting of pure drug particles typically below 1 µm in size, provide a greatly increased surface area that enhances saturation solubility and accelerates dissolution. Consequently, nanocrystals contribute to better bioavailability, reduced dose variation, and facilitate diverse administration routes such as oral, parenteral, and topical delivery. This review summarizes the underlying principles, advantages, and preparation techniques of nanocrystals including top-down, bottom-up, and hybrid methods along with recent advancements in nanocrystal-based systems for enhancing the performance of poorly soluble drugs.