title: Design and In Vivo Anti-Inflammatory Effect of Ketoprofen Delayed Delivery Systems.
abstract: For the treatment of inflammatory-based diseases affected by circadian rhythms, the development of once-daily dosage forms is required to target early morning symptoms. In this study, Zn-alginate beads containing ketoprofen (K) were developed by a tandem technique prilling/ionotropic gelation. The effect of main critical variables on particles micromeritics, inner structure as well as on drug loading and in vitro drug release was studied. The in vivo anti-inflammatory efficacy was evaluated using a modified protocol of carrageenan-induced edema in rat paw administering beads to rats by oral gavage at 0, 3, or 5 h before edema induction. Good drug loading and desired particle size and morphology were obtained for the optimized formulation F20. In vitro dissolution studies showed that F20 had a gastroresistant behavior and delayed release of the drug in simulated intestinal fluid. The in vitro delayed release pattern was clearly reflected in the prolonged anti-inflammatory effect in vivo of F20, compared to pure ketoprofen; F20, administered 3 h before edema induction, showed a significant anti-inflammatory activity, reducing maximum paw volume in response to carrageenan injection, whereas no response was observed for ketoprofen. The designed beads appear a promising platform suitable for a delayed release of anti-inflammatory drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3451-3458, 2015.
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerciello
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Auriemma
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Del Gaudio
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, University of Salerno, I-84084, Fisciano, (SA), Italy.
authors.forename: Rita P
authors.initials: RP
authors.lastname: Aquino
mesh_terms: D000284:Administration, Oral; D000464:Alginates; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002351:Carrageenan; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007660:Ketoprofen / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D000464:Alginates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D002351:Carrageenan; D007660:Ketoprofen
keywords: alginate; dissolution; microencapsulation; microparticles; oral drug delivery; polymeric drug delivery systems; solid dosage form