Effect of Penetration Enhancers and Safety on the Transdermal Delivery of Apremilast in Skin

Abstract

The poor water solubility of apremilast (APR) is the main impediment to the penetration of the drug through the skin barrier. The objective of this study was to evaluate the permeability of APR in different solutions enriched with penetration promoters in ex vivo samples of human skin, and additionally assess its tolerance in vivo. To this end, APR solutions with 5% promoter were developed, and the drug’s ability to penetrate human abdominal skin samples was evaluated; the coefficients of permeability, cumulated amounts permeated, and flow were some of the parameters evaluated; likewise, the in vitro and in vivo tolerance of the solutions was evaluated. The results obtained showed that the solutions containing squalene as a promoter improved the penetration of APR compared to the other promoters evaluated; in the same way, on an in vitro scale in HaCaT cells, the promoters were not toxic, finding a cell viability greater than 80% at the different dilutions evaluated. In the in vivo tests carried out with the solution that presented the best results (APR-Squalene solution), it was observed that it does not cause irritation or erythema on the skin after its colorimetric and histological evaluation of the dorsal region of rats after its application. Squalene becomes an excellent candidate to improve the permeability of the drug in the case of the development of a topical formulation; in addition, it was confirmed that this penetration enhancer is neither toxic nor irritating when in contact with the skin in in vivo tests.

Semi-Solid Dosage Forms Containing Pranoprofen-Loaded NLC as Topical Therapy for Local Inflammation: In Vitro, Ex Vivo and In Vivo Evaluation

“…The steady-state flux across the skin ( J ss , µg/h/cm 2 ) and the transdermal permeability coefficient ( K p , cm/s) were calculated according to the following equations [ 41 ]: in which Qt (μg) is the quantity (amount) of drug permeated across the skin and thus detected in the receptor chamber, A (cm 2 ) denotes the active cross-sectional area (accessible for diffusion), t (h) is the time of exposure, and C 0 is the primary drug concentration in the donor chamber.…”

“…The inflammatory process was induced topically by applying xylol to the right ear for 40 min [ 41 ]. Three inflamed mice were chosen as a group for the + control.…”

Gel-Dispersed Nanostructured Lipid Carriers Loading Thymol Designed for Dermal Pathologies

“…The donors provided written informed consent and the experimental protocol was approved by the Research Commission of Barcelona SCIAS Hospital (Barcelona, Spain). 46 , 47 The experimental procedure and quantitative analysis of TH were carried out according to a previously described method, with modifications. 31 , 48 This study consisted of three experiments set up to find comparable analysis and they were all performed in Franz cells using the same conditions described above.…”

Predicting skin permeation-enhancing effect of fixed oils using saturated to unsaturated fatty acid ratio content

“…This could be of concern when the drug is administered for a long-term (Zhai and Maibach, 2004). The development of penetration enhancers that are safe, compatible with the drug formulation, and do not cause skin irritation is a challenge (Sarango-Granda et al, 2022). Fatty acids are a class of substances that have been reported to cause little or no skin irritation in topical formulations.…”