Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods

Objectives Wet milling is a common technique to produce drug nanocrystals. Stability of the nanocrystals is a critical question, and different kinds of stabilizers, e.g. polymers, celluloses, surfactants and lipids, have been tested for various drugs. Still, the question about how to select the best stabilizer to a certain drug material and also to a selected process is open. Key findings Many different factors, such as surface energy, hydrophobicity, solubility, viscosity and functional groups, affect the stability of the formed nanosuspensions. Affinity of the stabilizer to the particle surfaces seems to be the most important parameter. This affinity is partly related to the surface energy and hydrophobicity of the surfaces and stabilizers. Summary In this review the most important factors affecting nanocrystal formulation and efficacy of stabilizers are presented. In order to widen understanding of the milling process, the most important variables related to milling techniques and particle fracturing processes during the milling are briefly presented.