Formulation and Optimization of Celecoxib-Loaded Microspheres Using Response Surface Methodology

Purpose: To employ response surface methodology (RSM) for statistical optimization of formulation factors in the preparation of celecoxib-loaded microspheres.
Methods: Celecoxib microspheres were prepared by solvent evaporation method. Biodegradable/biocompatible polymers, Eudragit L-100 and polyvinyl pyrrolidone, were used in the encapsulation procedure. A central composite design employing Stat-Ease design Expert^®, version 7.0.3 having a unit value of α was used according to reference protocols to assess the influence of two independent variables (i.e., the concentration of the two polymers used) on four dependent variables (i.e., recovery, encapsulation efficiency and % drug releasred). The polymers used were Eudragit-L100 (X₁) and polyvinyl pyrrolidone (X₂). The microspheres were characterized for size, shape, recovery (%), entrapment efficiency and drug release.
Results: The recovered total weight of microspheres ranged between 49.4 ± 3.1 and 91.1 ± 4.8 %, and it decreased with increase in the concentration of PVP. Entrapment efficiency was in the range of 54.1 ± 2.9 to 95.6 ± 3.7 %, and was also dependent on polymer concentration. The release of celecoxib increased with decrease in Eudragit L-100 concentration and increase in PVP concentration. Higuchi model was the best-fit drug release from all the formulations. Korsemeyer-Peppas release exponent (n) indicates that drug release pattern was non-Fickian diffusion.
Conclusion: Using RSM, it is possible to optimize the drug release properties of celecoxib-loaded microspheres. A celecoxib-loaded microsphere formulation with optimum recovery, entrapment efficiency and release behavior was proposed.

Keywords
Celecoxib, Eudragit L-100, Polyvinyl pyrrolidone, Response surface methodology, Microspheres.