Pharmaceutical nanocrystals: production by wet milling and applications

Nanocrystals are regarded as an important nanoformulation approach exhibiting advantages of increased dissolution and saturation solubility with chemical stability and low toxicity. Nanocrystals are produced in the form of nanosuspensions using top-down (e.g., wet milling or high pressure homogenization) and bottom-up methods (e.g., antisolvent precipitation). Wet milling is a scalable method applicable to drugs with different physicochemical and mechanical properties. Nanocrystalline-based formulations, either as liquid nanosuspensions or after downstream processing to solid dosage forms, have been developed as drug delivery systems for various routes of administration (i.e., oral, parenteral, pulmonary, ocular, and dermal). In this review, we summarize and discuss the features, preparation methods, and therapeutic applications of pharmaceutical nanocrystals, highlighting their universality as a formulation approach for poorly soluble drugs