Exploring potential of diacerin nanogel for topical application in arthritis: Formulation development, QbD based optimization and pre-clinical evaluation

Abstract

Diacerein (DCN) is a chondroprotective agent which shows inadequate oral bioavailability along with gastrointestinal side effects. This study is intended to develop a topical novel DCN delivery system. DCN nanogel was prepared by emulsion solvent diffusion technique. The formulation was optimized by response surface methodology by taking two independent variables, concentration of carbopol 940 and eudragit RSPO and three dependent variables, particle size, % entrapment efficiency (EE) and % drug release at 24 h. The optimized formulation had adequat% EE, % drug release at 24 h and particle size. The particle size for optimized nanogel was 190.3 nm with % EE of 83.51% whereas % drug release at 24 h was found 90.13%. The optimized DCN nanogel was analyzed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (DTIR) and transmission electron microscopy (TEM) studies. The drug release kinetic study has shown that the gel followed Higuchi’s model and the diffusion was anomalous in nature. The nanogel was characterized for physical examination, viscosity, homogeneity and stability parameters and the results obtained were found upto the mark. The ex-vivo permeation study data was in correlation with results of in-vitro study. In-vivo anti-arthritic study proved the efficacy of developed formulation for arthritis in Freund’s Adjuvant Arthritic model. This research work has proved the significant potential of innovated product for arthritis by topical route, as it overcomes the drawbacks of oral route, highly efficient, sustained and targeted the release of drug without any accumulation and toxicity.