Development of gelatin microspheres loaded with diclofenac sodium for intra-articular administration

We have previously reported on the targeting of diclofenac sodium in joint inflammation using gelatin
magnetic microspheres. To overcome complications in the administration of magnetic microspheres and
achieve higher targeting efficiency, the present work focuses on the formulation of gelatin microspheres
for intra-articular administration. Drug-loaded microspheres were prepared by the emulsification/crosslinking method, characterized by drug loading, size distribution, scanning electron microscopy (SEM), Fourier
transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gas
chromatography, and in vitro release studies. The targeting efficiency of microspheres was studied in vivo
in rabbits. The microspheres showed drug loading of 9.8, 18.3, and 26.7% w/w with an average size range
of 37–46 µm, depending upon the drug–polymer ratio. They were spherical in nature and free from surface
drug as evidenced by the SEM photographs. FT-IR, DSC, and XRD revealed the absence of drug–polymer
interaction and amorphous nature of entrapped drug. Gas chromatography confirms the absences of residual glutaraldehyde. The formulated microspheres could prolong the drug release up to 30 days in vitro. About
81.2 and 43.7% of administered drug in the microspheres were recovered from the target joint after 1 and
7 days of postintra-articular injection, respectively, revealing good targeting efficiency.