Biodegradable gelatin microspheres as controlled release intraarticular delivery system: The effect of formulation variables

Abstract

Intraarticular administration of microspheres containing non-steroidal antiinflammatory drugs is beneficial in the treatment of rheumatoid arthritis. Microspheres could localize drug at the site of administration and control its release, resulting in improved therapeutic effects and decreased side effects. Therefore, the objective of the present study was to prepare controlled release meloxicam-loaded gelatin microspheres and evaluate the effect of various variables on their properties. Meloxicam-loaded microspheres were prepared by emulsion-congealing-chemical cross-linking method. Different amounts of polymer, emulsifier and crosslinking agent, as formulation variables, were evaluated. Microspheres were characterized in terms of yield value, encapsulation efficiency and the drug release pattern. The particle size, surface morphology and thermal behaviour of microspheres were also investigated. According to the results, using glutaraldehyde as a cross-linking agent resulted in spherical microspheres with the yield value of 63-96% and encapsulation efficiency of 23-63%. The optimum formulation with the mean particle size of about 57 μm, showed slow drug release profile (64%) throughout 48 h. An appropriate polymer:cross-linker ratio must be used to obtain suitable particles with acceptable controlled released behaviour. In summary the results of the present study supported the preparation of sustained release meloxicam-loaded microspheres using emulsion-congealing method along with the potential application of glutaraldehyde in improving the physical properties of prepared particles as well as the release profile of this low water soluble drug.