Effect of powder processing on performance of fenofibrate formulations

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 69; no. 2; pp. 727 - 734
• Main Authors: Jain, Rajeev A., Brito, Luis, Straub, Julie A., Tessier, Todd, Bernstein, Howard
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.06.2008; Elsevier Science
• Subjects: Biological and medical sciences; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Drug Compounding - instrumentation; Fenofibrate; Fenofibrate - administration & dosage; Fenofibrate - chemistry; General pharmacology; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - chemistry; Jet-milling; Kinetics; Medical sciences; Microscopy, Electron, Scanning; ODTs; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poorly soluble; Powders; Solubility; Tablets; ODTs; Fenofibrate; Poorly soluble; Jet-milling; Performance evaluation; Pharmaceutical technology; Fibrate derivatives; Formulation; Performance; Powder; Antilipemic agent
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2007.12.006

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.