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/cross-linking 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.
Saravanan
Muniyandy
M
Medicine and Health Sciences, Monash University, Selangor Darul Ehsan, Malaysia. msaravanan72@hotmail.com
Bhaskar
Kesavan
K
Maharajan
Gomathinayagam
G
Pillai
Kalathil Sadasivan
KS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005780:Gelatin / Q000737:chemistry; D005976:Glutaral / Q000737:chemistry; D007270:Injections, Intra-Articular; D008863:Microspheres; D010316:Particle Size; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004008:Diclofenac; D005780:Gelatin; D005976:Glutaral