Diclofenac sodium pellets for flexible pediatric drug dosing: Preparation, characterization and evaluation

The objective of the current investigation was to formulate Eudragit RS100 based sustained release pellets, containing Diclofenac sodium intended for flexible dosing in pediatric patients. Diclofenac sodium is a type II antiinflamatory agent. Pellets in the form of microspheres were prepared by O/O emulsion solvent evaporation method with different stabilizer concentrations and at different speeds of emulsification while maintaining constant amounts of Diclofenac sodium. Span 80 was used as the stabilizer. Drug excipient compatibility study was performed prior to formulation development and only compatible excipients were used in the fabrication of microspheres. Prepared microsphere formulations were characterized for percentage yield, particle size analysis, entrapment efficiency, invitro release behavior, differential scanning colorimetry (DSC), scanning electron microscopy (SEM), in vivo drug release and in vitro in vivo correlation (IVIVC). SEM studies showed that the microspheres were spherical with rough surface morphology. The drug loaded microspheres showed 50-80% entrapment efficiency. The invitro release profile showed a slow and steady release pattern for Diclofenac sodium. A 100% Diclofenac sodium was released within a period of 12 hrs during this time. The drug release was found to follow diffusion controlled mechanism. The n value of Korsmeyer Peppas equation indicated non Fickian type of diffusion. DSC results indicated that the physical state of the drug was changed upon fabrication. In rats, the pellets released the drug for over a period of 12 hrs after oral administration. A 100% IVIVC was achieved with the optimized formulation. As a result of these experiments, it was concluded that, novel sustained release oral pellets comprising of diclofenac sodium were successfully prepared using eudragit RS100 as the polymer and using emulsion solvent evaluation method.