The application of freeze-drying as a production method of drug nanocrystals and solid dispersions – A review

This work reviews the examples of the application of lyophilization and its cryogenic modifications as the production method of solid dispersions and drug nanocrystals, two formulation approaches aimed at increasing the solubility, dissolution rate and oral bioavailability of poorly water soluble drugs. A brief recapitulation of freeze-drying basics is presented and the review is organized according to application and product type, with the consideration of different cryogenic techniques, e.g. spray freezing into liquid, as well as the combinations of lyophilization with other nanonization methods in pharmaceutical technology. The review focuses on freeze-drying as a particle engineering tool for the size reduction and surface area enhancement in the generation of nanosized drug particles, both as simple nanocrystals and as their dispersions within water soluble micro- or nanoparticulate matrices, instead of the use of lyophilization as a mere drying or solidification method. Therefore, attention is given to the relationships between formulation and process parameters (e.g. freezing rate), and the properties of the obtained material: particle size, porosity, surface area, morphology, polymorphism and dissolution behavior.