No 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.

Local delivery of imidazolic antifungals is limited by its extreme lipophilicity. Multiple emulsions (ME) are a potential vehicle to enhance the delivery of econazole nitrate (ECN), an antifungal targeted to deep-seated epidermal yeast infections. An 1% ECN hydrophilic ME was compared with a commercial formulation in terms of rheology, droplet size and in vitro antifungal activity against Candida species. Comparative in vitro drug release, human skin permeation and drug retention were investigated using vertical diffusion cells. Rheology demonstrated a pseudoplastic shear thinning with thixotropy facilitating skin residence. No significant aggregation or droplet size variations were observed during a 6-month stability storage. Both formulations exhibited similar release levels achieving asymptotic values in 5 h. ECN skin permeation levels from the multiple emulsion resulted to be significantly higher than those of the commercial formulation, attributable to differences in formulation polarity and excipients composition. Conversely, similar drug accumulation levels in skin were obtained (40-130 ppm). These concentrations resulted to be comparable with obtained MIC values (2-78 ppm), confirming the in vitro antimicrobial efficacy of both formulations. A similar skin retention and a higher permeation rate over the existing formulations is considered an improved approach to target the drug to deep epidermis.

Optimization of transdermal formulations requires solving simultaneous challenges as the selection of release polymers. The interactions between the formulation components must be taken as a way to modulate its performance. Selection of acrylic polymers with different functionalizations for the transdermal formulation of a tertiary amine drug (ropinirole HCl) have been investigated. Aim of this work is to characterize the influence over drug release of certain experimental interactions. Solubility-crystalization and pharmacopoeial release tests have been used to evaluate the influence of drug loading and the pH of the release media. Area under the curve of dissolved amounts and percentage of release have been used as discriminant variables in mutual influence with the physical state of the drug. Elucidation of release mechanisms has been performed with data fitting of relevant modelystic equations. Fickian release and erosion contribution have been related with drug loading and the risk of burst effects. In conclusion, a rationale to select the best suitable polymer for ropinirole HCl has been demonstrated in terms of efficiency and extent of release.