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 50 °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.