Pharmaceutical Cryogenic Technologies

Poor bioavailability associated with poorly water-soluble compounds remains a challenging issue in drug development. Particle engineering may be used to improve the physicochemical properties of poorly water-soluble compounds, thereby enhancing the bioavailability. Cryogenic technologies, including spray freeze drying (SFD), spray freezing into liquid (SFL), and thin film freezing (TFF), are "bottom-up" precipitation processes to generate amorphous nanostructured aggregates with significantly enlarged surface area, higher dissolution rates, and supersaturation, via rapidly inducing nucleation followed by particle growth arrest through stabilization via polymers and solidification of the solvent. This chapter provides detailed description of each cryogenic process, formulation guidelines, and characterization analyses. Finally, examples of cryogenically engineered drug compositions with improved in vitro and in vivo macroscopic performance are provided to illustrate the potential benefits of cryogenic technologies, especially TFF.