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 ¹³C-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).

Keywords::

• Genipin
• gelatin microspheres
• intra-articular delivery
• flurbiprofen
• biocompatibility
• retention efficiency

Acknowledgements

The authors are grateful to Sun Pharmaceutical Industries Ltd., Ahmednagar, India for providing flurbiprofen as a gift sample and Microtrol Sterilization Services Pvt. Ltd., Bangalore, India for Gama sterilization of microspheres. Jitendra Kawadkar expresses his sincere thanks to Govt. of National Capital Territory of Delhi, New Delhi, India for awarding the Senior Research Fellowship during his PhD program.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.