A New Low Melting-Point Polymorph of Fenofibrate Prepared via Talc Induced Heterogeneous Nucleation

Fenofibrate is one of the most commonly prescribed hyperlipidemia agents. Despite its high lipophilicity and ultralow aqueous solubility, most commercially available formulations use micronized crystalline fenofibrate form I, which has a low dissolution rate and poor oral bioavailability. Little is known about the crystallization of other polymorphs from supercooled amorphous fenofibrate. This study reports a new fenofibrate polymorph (form III) obtained via a controlled heterogeneous nucleation method using low quantity (1% w/w) of the generally recognized as safe (GRAS) oral pharmaceutical excipient talc. Form III has a low melting point of SO degrees C, and crystallization of form I immediately occurs after the melting of form III. The microscopic, thermal, and spectroscopic characterizations of form III confirmed the distinct molecular packing difference between the new form and other known forms. The discovery of this new form will enrich the understanding of the molecular behavior of fenofibrate and bring useful insights into the role pharmaceutical excipients in selective crystallization of pharmaceutical active ingredients.