Third-Generation Transdermal Delivery Systems Containing Zidovudine: Effect of the Combination of Different Chemical Enhancers and a Microemulsion System

Abstract

This study aimed to examine the influence of the combination of chemical enhancers and a microemulsion on the transdermal permeation of zidovudine (AZT). Ethanol, 1,8-cineole, and geraniol were incorporated in a microemulsion. The droplet size, zeta potential, rheology, and SAXS analysis were performed. The permeation enhancer effect was evaluated using pig ear skin. Snake skin (Boa constrictor) treated with the formulations was also used as a stratum corneum model and studied by attenuated total reflectance-infrared spectroscopy. As a result, it was observed that the incorporation of the chemical enhancers promoted a decrease of the droplet size and some rheological modifications. The 1,8-cineole associated with the microemulsion significantly increased the permeated amount of AZT. Conversely, ethanol significantly increased the quantity of the drug retained in the skin. The probable mechanism for the cineole and ethanol effects was respectively: fluidization and increasing of the diffusion coefficient, and increasing of the partition coefficient. Surprising, geraniol + microemulsion drastically decreased both the permeated and the retained amount of AZT into the skin. Thus, the adequate association of microemulsion and chemical enhancers showed to be a crucial step to enable the topical or transdermal use of drugs.

Transcutol® P/Cremophor® EL/Ethyl Oleate–Formulated Microemulsion Loaded into Hyaluronic Acid–Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen

“…Nanocarriers and the chemical permeation enhancers can effectively promote penetration with convenient application. In recent years, microemulsion has been widely used in transdermal drug administration due to its prominent penetration-promoting effect (5)(6)(7)(8)(9)(10).…”

Transdermal delivery systems in cosmetics

“…Where synergistic effects can be obtained, the combinatorial approach has the potential for effective permeation enhancement at lower active concentrations than separate approaches (du Toit et al 2016). For example, the study by Carvalho et al (2018) about the combination of chemical enhancers incorporated a microemulsion of ethanol, 1,8-cineole, and geraniol and showed that the ethanol and cineole causes an increase in the diffusion and partition coefficients. Karande et al (2004) proposed an experimental tool, in vitro skin impedance guided by highthroughput screening, to investigate particular mixtures of penetration enhancers for increased skin permeability to macromolecules (~10 kDa), which yielded up to~100fold enhancement without inducing skin irritation.…”

Microemulsions and Nanoparticles as Carriers for Dermal and Transdermal Drug Delivery

“…Also, the microemulsions that contained a high eugenol concentration and Polyethylene Glycol (PEG) were able to increase the loading capacity of indomethacin as evidenced by a significant improvement in the solubility of the drug in these formulations compared to its water solubility (logP of indomethacin=4.46). In another study, ME was prepared with cineole as a chemical enhancer, a combination that promoted a higher skin permeation of zidovudine [67]. Zidovudine, a poorly bioavailable drug with a short half-life of 0.53h, significantly permeated through pig ear skin and snake skin from the cineole containing ME (by threefold) compared with the control.…”