title: Formulation and evaluation of flurbiprofen-loaded genipin cross-linked gelatin microspheres for intra-articular delivery.
abstract: Oral and parenteral formulations are challenging to produce therapeutic concentration of flurbiprofen in the joints. This encourages for the development of formulation for long term drug retention in the joint through intra-articular (i. a.) administration. In this study, genipin cross-linked gelatin microspheres of flurbiprofen were prepared for i. a. delivery. The microspheres were prepared using emulsification-homogenization-cross-linking method by changing the experimental variables such as concentration of cross-linker, cross-linking time and cross-linking temperature. The microspheres showed drug entrapment up to 76.19% with a mean particle size range of 5.91-8.19 µm. The degree of cross-linking and water-soluble fraction were 8.27-59.33% and 12.29-81.23%, respectively. SEM confirmed smooth surface and spherical shape of the microspheres. FTIR and (13)C-NMR confirmed cross-linking of gelatin by genipin. No chemical change in encapsulated drug was observed by FTIR and TGA. DSC and XRD indicated the molecular dispersion of drug within microspheres. Optimized microspheres could prolong the drug release for more than 108 h with anomalous transport. Histopathology confirmed the biocompatibility of microspheres in the rat (Wistar) knee joint. After 96 h of i. a. injection, significant higher amount (42.56%) of administered drug in cross-linked microspheres was recovered than uncross-linked microspheres (8.27%) confirming better drug retention efficiency (p < 0.01).
authors.affiliation: Department of Pharmaceutics, NDDS Research Laboratory, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), University of Delhi, New Delhi, India.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Kawadkar
authors.forename: Ritika
authors.initials: R
authors.lastname: Jain
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
authors.forename: Ashwinkumar
authors.initials: A
authors.lastname: Pathak
authors.forename: Meenakshi Kanwar
authors.initials: MK
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D001672:Biocompatible Materials / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D039823:Iridoids / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D039823:Iridoids; D005480:Flurbiprofen; C007834:genipin