title: Effect of powder processing on performance of fenofibrate formulations.
abstract: In this study, the effect of the order in which powder blending and jet-milling were performed for the production of the bulk powders on the performance of 200-mg dose orally disintegrating tablets (ODTs) of fenofibrate was evaluated. Bulk powders composed of fenofibrate, mannitol, copovidone S630, and docusate sodium in a 10:10:2:1.2 ratio were prepared by the following three processes: process A: fenofibrate+excipients-->blending; process B: fenofibrate-->jet-milling-->blending with excipients; process C: fenofibrate+excipients-->blending-->jet-milling. The bulk powders were granulated followed by blending and tableting. The materials were tested for Differential Scanning Calorimetry (DSC), drug particle sizing post-reconstitution, dissolution, optical micrography, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS) and disintegration of the ODTs. It was found that the crystallinity of fenofibrate was not impacted by the blending and jet-milling processes. Process A produced materials having poorer fenofibrate reconstitution as compared to processes involving jet-milling. It was discovered that milling a blend of fenofibrate/excipient (process C) was advantageous over milling the raw drug alone (process B). Process C yielded bulk powder that showed rapid dissolution and ODTs which exhibited rapid disintegration.
authors.affiliation: Acusphere, Inc, Formulation Support and Pharmaceutics, 500 Arsenal Street, Watertown, MA 02472, USA. jain@acusphere.com <jain@acusphere.com>
authors.forename: Rajeev A
authors.initials: RA
authors.lastname: Jain
authors.forename: Luis
authors.initials: L
authors.lastname: Brito
authors.forename: Julie A
authors.initials: JA
authors.lastname: Straub
authors.forename: Todd
authors.initials: T
authors.lastname: Tessier
authors.forename: Howard
authors.initials: H
authors.lastname: Bernstein
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000295:instrumentation; D011345:Fenofibrate / Q000008:administration & dosage* / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013607:Tablets
chemical_list: D000960:Hypolipidemic Agents; D011208:Powders; D013607:Tablets; D011345:Fenofibrate