Development, QbD based optimization and in vitro characterization of Diacerein loaded nanostructured lipid carriers for topical applications

Abstract

ObjectiveDCN is a chondro-protective agent which displays inadequate oral bioavailability along with gastrointestinal side effects. It is a choice of drug for treatment of osteoarthritis. Therefore, the objective of this study was to develop and optimize DCN loaded nanostructured lipid carrier (NLCs) for topical delivery. MethodNLCs were prepared by hot homogenization followed by sonication method. The formulation was optimized by 2 factor 3 level central composite design taking two independent variables i.e. concentration of stearic acid (A) and concentration of oleic acid (B), and three independent variables, particles size (Y1), % entrapment efficiency (Y2) and % drug release at 24 hours(Y3). ResultThe particle size, % entrapment efficiency and in-vitro drug release at 24 hours of optimized formulation was found 173.76 nm, 91.30%, and 94.17% respectively. The optimized DCN-NLC formulations were analyzed by DSC and XRD, TEM, and FTIR studies. DCN-NLC loaded gel was prepared and characterized for physical examination, viscosity and stability parameters. DCN-NLC in the gel form displayed sustained drug release and significant (p<0.05) tissue penetration in vitro in comparison to plain gel and DCN solution. The drug release kinetics study illustrated the Higuchi’s release pattern for prolonged period of time. Ex vivo permeation study result supported good topical penetration for DCN using DCN-NLCs. ConclusionConclusively, the developed formulation has potential for topical application for future pre-clinical studies.