Voriconazole loaded nanostructured lipid carriers based topical delivery system: QbD based designing, characterization, in-vitro and ex-vivo evaluation

Abstract

Clinical investigation showed that voriconazole exhibits various adverse effects such as nausea, vomiting, and other gastric disturbances. To overcome these associated side effects, nanostructured lipid carriers (NLCs) embedded topical formulation was developed for voriconazole delivery to the topical site which can minimize the frequency and intensity of associated adverse effects. In the current study, QbD (Quality by Design) based risk assessment was exploited for the preparation of voriconazole loaded NLCs. The Box-Behnken design was utilized for risk assessment and optimization for various formulation and process parameters. Two central points were utilized in design for the accomplishment of the goal. The optimized formulation showed mean particle size 107.7 ± 8 nm with 70.52 ± 5%, entrapment efficiency and 6.59% drug loading. In-vitro drug release study revealed the prolong release of voriconazole for 10 h. The selected formulation was loaded into carbopol gel and the ex-vivo permeation studies of NLCs loaded gel showed improved permeation (66.45%) and sustained release up to 11 h compared to free drug based gel. The NLCs embedded gel could retain more amount of drug in the skin layers indicated its reduced systemic access and can minimize the side effects associated with free drug. In-vitro antifungal study on Aspergillusflavus culture showed 22.5 ± 0.5 mm zone of inhibition with NLCs formulation whereas free drug showed the only 14.5 ± 0.5 mm. QbD assimilated approach for formulation optimization helped in the understanding interaction between process and formulation parameters. Thus, the prepared NLCs gel could target skin and could be a potential alternative for treating topical fungal infections in the future.