Crystallization of undercooled liquid fenofibrate.
Formulation of hydrophobic drugs as amorphous materials is highly advantageous as this increases their solubility in water and therefore their bioavailability. However, many drugs have a high propensity to crystallize during production and storage, limiting the usefulness of amorphous drugs. We study the crystallization of undercooled liquid fenofibrate, a model hydrophobic drug. Nucleation is the rate-limiting step; once seeded with a fenofibrate crystal, the crystal rapidly grows by consuming the undercooled liquid fenofibrate. Crystal growth is limited by the incorporation of molecules into its surface. As nucleation and growth both entail incorporation of molecules into the surface, this process likely also limits the formation of nuclei and thus the crystallization of undercooled liquid fenofibrate, contributing to the good stability of undercooled liquid fenofibrate against crystallization.
School of Engineering and Applied Sciences, Harvard University, 02138 Cambridge, Massachusetts, USA. weitz@seas.harvard.edu.
Esther
E
Amstad
Frans
F
Spaepen
David A
DA
Weitz
D003460:Crystallization; D011345:Fenofibrate / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning
D000960:Hypolipidemic Agents; D011345:Fenofibrate