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. 2021 Mar 16;26(6):1650.
doi: 10.3390/molecules26061650.

Effect of Penetration Enhancers on Toenail Delivery of Efinaconazole from Hydroalcoholic Preparations

Jun Soo Park  1 , Jeong Soo Kim  2 , Myoung Jin Ho  1 , Dong Woo Park  1 , Eun A Kim  1 , Yong Seok Choi  1 , Sun Woo Jang  2 , Myung Joo Kang  1
Affiliations

Effect of Penetration Enhancers on Toenail Delivery of Efinaconazole from Hydroalcoholic Preparations

Jun Soo Park et al. Molecules. .

Abstract

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.

Keywords: bovine hoof; efinaconazole; hydroalcoholic solution; hydroxypropyl-β-cyclodextrin; onychomycosis; permeation enhancer; propylene glycol dicaprylocaprate; transungual drug delivery.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structure of efinaconazole.
Figure 2
Figure 2
In vitro permeation profile of efinaconazole through the bovine hoof from L-hydroalcoholic solutions (HSs) with different lipophilic enhancers in the Franz diffusion cell model. Data represent mean ± standard deviation (n = 4).
Figure 3
Figure 3
In vitro permeation profile of efinaconazole through the bovine hoof from LH-HS preparations prepared with different hydrophilic enhancers, along with Labrafac PG as a lipophilic enhancer in the Franz diffusion cell model. Data represent mean ± standard deviation (n = 4).
Figure 4
Figure 4
In vitro permeation profile of efinaconazole through the bovine hoof from oil solutions (OSs) prepared with different oily vehicles in the Franz diffusion cell model. Data represent mean ± standard deviation (n = 3).
See this image and copyright information in PMC

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