TY - JOUR

T1 - Design and evaluation of microemulsion-based efinaconazole formulations for targeted treatment of onychomycosis through transungual route

T2 - Ex vivo and nail clipping studies

AU - Agrawal, Vikas

AU - Patel, Rashmin

AU - Patel, Mrunali

AU - Thanki, Kaushik

AU - Mishra, Sandip

PY - 2021

Y1 - 2021

N2 - The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul? MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol? (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol? P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudoternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol? 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36?12.90?gcm? 2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.

AB - The onychomycosis treatment remains a big challenge for onychologist due to the shorter nail residence time of topical formulations and the lack of availability of novel formulations in markets for new generation antifungal drugs. The objective of this work was to design, develop, optimize, and evaluate microemulsion formulations for effective delivery of efinaconazole through transungual route in onychomycosis treatment. Capmul? MCM (Glyceryl Caprylate/Caprate) as oil, Labrasol? (caprylocaproyl polyoxyl-8 glycerides) as a surfactant, and Transcutol? P (diethylene glycol monoethyl ether) as co-surfactant exhibited higher solubility of efinaconazole and surfactant-cosurfactant mixture (Smix) in a ratio of 1:1 rendered higher microemulsion region in the pseudoternary phase diagram. The optimized microemulsion formulation containing 6%w/w oil phase, 22.5%w/w surfactant, 22.5%w/w co-surfactant, and 49%w/w demineralized water was converted into gel formulation using 1.0%w/w Carbopol? 934 P gelling agent and evaluated for stability of 6 months. The optimized microemulsion formulation globule size was less than 100 nm. The ex vivo permeation confirmed improved permeation of efinaconazole from microemulsion formulations (346.36?12.90?gcm? 2) in comparison to reference formulation without observing any lag in drug permeation through the nail plate. The in vitro antifungal study data indicated increased antifungal efficacy relative to efinaconazole topical solution against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans species. Further, an in vitro cell cytotoxicity study exhibited no toxic effect for any excipients used in the formulation while applied on nail cells. Hence, the efinaconazole loaded microemulsion formulations could be considered as an effective therapy in the treatment of onychomycosis.

KW - Efinaconazole

KW - Onychomycosis

KW - Microemulsion-gel

KW - Nail clipping study

KW - Transungual delivery

U2 - 10.1016/j.colsurfb.2021.111652

DO - 10.1016/j.colsurfb.2021.111652

M3 - Journal article

C2 - 33740733

VL - 201

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

M1 - 111652

ER -