Abstract
Efficient topical delivery of imidazolic antifungals faces the challenge of overcoming its limited water solubility and its required long-lasting duration of treatments. In this paper, a hydrophilic multiple emulsion (ME) of Bifonazole (BFZ) is shown to maximize its skin retention, minimize its skin permeation, and maintain an acceptable level of being harmless in vivo. The formulations were pharmaceutically characterized and application properties were assessed based on viscosity measurements. Non-Newtonian pseudoplastic shear thinning with apparent thixotropy was observed, facilitating the formulation retention over the skin. The in vitro release profile with vertical diffusion cells showed a predominant square-root release kinetic suggesting an infinite dose depletion from the formulation. Ex vivo human skin permeation and penetration was additionally evaluated. Respective skin permeation was lower than values obtained with a commercial O/W formulation. The combination of amphoteric and non-ionic surfactants increased the bifonazole epidermal accumulation by a factor of twenty. This fact makes the possibility of increasing its current 24 h administration frequency more likely. Eventual alterations of skin integrity caused by the formulations were examined with epidermal histological analysis and in vivo preclinical measurements of skin elasticity and water retrograde permeation. Histological analysis demonstrated that the multiple emulsions were harmless. Additionally, modifications of in vivo skin integrity descriptors were considered as negligible.
Highlights
Bifonazole [1-[[1,1’-biphenyl)-4-phenylmethyl]-1H-imidazole) (BFZ) is an imidazolic antifungal drug indicated against skin or mucosal mycoses
Several formulation strategies, such as the hydrophilic W/O/W multiple emulsions (ME), can expedite this skin accumulation: They consist of two hydrophilic internal and external phases separated by a lipophilic layer that dissolves hydrophobic drugs and incorporates them into a hydrophilic formulation
W/O/W emulsions were prepared with a two-step emulsification method and were physically characterized with optical examination, laser and microscopic droplet size distribution, rheological studies, pH and conductimetric analyses, and they were tested for drug content
Summary
Bifonazole [1-[[1,1’-biphenyl)-4-phenylmethyl]-1H-imidazole) (BFZ) is an imidazolic antifungal drug indicated against skin or mucosal mycoses. Formulations for local therapy are desirable in order to achieve the highest drug penetration deep into the epidermis, which is the site of action. These drugs are markedly lipophilic and are largely retained in the stratum corneum (SCR) [3], making the treatment of deep-seated epidermal infections more difficult. Topical agents, which are conventionally used for the treatment of skin fungal infections, are usually formulated as creams, lotions, or gels Several formulation strategies, such as the hydrophilic W/O/W multiple emulsions (ME), can expedite this skin accumulation: They consist of two hydrophilic internal and external phases separated by a lipophilic layer that dissolves hydrophobic drugs and incorporates them into a hydrophilic formulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
