Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s).

Present study was designed to prepare and characterize aceclofenac loaded nanostructured lipid carriers (NLCs) employing Quality by Design (QbD)-oriented approach. The NLCs were evaluated for their transdermal penetration potential and stability. Aceclofenac loaded nanostructured lipid carriers (NLCs) were prepared & characterized, by employing Quality by Design (QbD)-oriented approach and further evaluated for transdermal penetration potential and stability. Different lipids and surfactants were chosen to prepare NLCs using microemulsion method as critical material attributes (CMAs). A 33 factorial design was used for optimization of NLCs, and evaluating them for different critical quality attributes (CQAs), viz. particle size, polydispersity index (PDI), zeta potential, in vitro drug release, entrapment efficiency. The effect of CMAs such as lipids, oil: lipid ratio and concentration of surfactants on CQAs viz. drug entrapment efficiency and particle size were systematically evaluated to optimize NLCs. The optimized NLCs were further incorporated into carbopol gel and characterized for texture and rheology profile followed by in vitro and in vivo evaluations. The optimized ACE-NLCs were found to be spherical, nanometric in size with higher drug loading and entrapment efficiency. Results of the in vitro drug release study showed that the developed formulation followed Korsmeyer-Peppas model showing Fickian diffusion. The release was biphasic i.e., initial burst release followed by sustained drug release upto 48h. The optimized NLCs-based gel formulation showed superior texture, rheological profile and showed better cell uptake efficiency on hyperkeratinocytic cells (HaCaT cell lines) with higher ex vivo skin permeability efficiency vis-à-vis marketed formulation. In conclusion, dermatokinetic modeling and pharmacodynamic study using carrageenan induced edema mice suggests that aceclofenac loaded NLCs hydrogel may provide a better delivery alternative to target various skin layers.