title: In vitro and in vivo evaluations of ketoprofen extended release pellets prepared using powder layering technique in a rotary centrifugal granulator.
abstract: In the present study, an extended release pellet dosage form of ketoprofen was prepared using powder layering technique. A combination of ethyl cellulose (45 cps) and shellac polymers was used as a binder (12% w/w polymer) during drug layering and an extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer) within the same apparatus. The coated pellets were characterized for sphericity, Hardness-Friability Index, and drug content, and also underwent scanning electron microscopy. In vitro dissolution was performed in 900 mL of phosphate buffer (pH 6.8) using paddle apparatus at 100 rpm. Ethyl cellulose and shellac when used as binders during drug loading did not extend ketoprofen release beyond 3 h. However, coating of the drug loaded pellets using ethyl cellulose and shellac resulted in an extended release profile of about 10 h. Using Higuchi's model and the Korsmeyer equation, the drug release mechanism from the pellets was found to be an anomalous type involving diffusion and erosion. Scanning electron microscopy was used to visualize the pellet morphology and drug release mechanism during dissolution testing. In vivo evaluations of the extended release pellets in rats indicated a significant increase in the time to reach maximum concentration (t(max)) and extent of absorption (AUC(0-∞)) compared to the ketoprofen immediate release tablet blend dispersed and dosed. In conclusion, extended release pellets of ketoprofen could perform therapeutically better than conventional dosage forms, leading to improved efficacy for a prolonged period.
authors.affiliation: Formulation Development Services, Matrix Laboratories Ltd., a Subsidiary of Mylan Laboratories Inc., Plot No 34A, Bollaram Industrial Area, Jinnaram Mandal, Medak District, Hyderabad 502325, India. raveendrapai@yahoo.co.in
authors.forename: Raveendra
authors.initials: R
authors.lastname: Pai
authors.forename: Kanchan
authors.initials: K
authors.lastname: Kohli
authors.forename: Gaurav
authors.initials: G
authors.lastname: Jain
authors.forename: Birendra
authors.initials: B
authors.lastname: Srivastava
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004343:Drug Implants; D006245:Hardness Tests; D006863:Hydrogen-Ion Concentration; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013607:Tablets
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011208:Powders; D013607:Tablets; D007660:Ketoprofen