Background: Tretinoin (TRE) is, for its anti-comedogenic and comedolytic activity, widely used in the topical treatment of acne vulgaris. The effect lies in the regulation of sebum production and collagen synthesis. The study is devoted to the formulation of dermal gels containing TRE using microemulsion as the drug solubilizer. Methods: The aim was to evaluate the effect of the reference microemulsion (ME) and lecithin-containing microemulsion (MEL) on the release of TRE through the synthetic membrane (in vitro) and the pig’s ear skin (ex vivo) through the Franz cell diffusion method. Subsequently, after an ex vivo study, the amount of the drug in the skin influenced by the applied formulation was determined. In addition, the impact of ME on the microscopic structure, texture, and rheological properties of gels was evaluated. Results: On the basis of the analysis of texture, rheological properties, and drug release studies, Carbopol formulations appear to be more appropriate and stable. Considering the synthetic membrane as a stratum corneum, the Carbopol gel penetrated about 2.5-higher amounts of TRE compared to the Xanthan gel. In turn, ex vivo studies suggest that MEL slows the drug transfer to the dissolution medium, simulating absorption into the blood, which is a desirable effect in local treatment. The drug retention study proved the highest amounts of TRE in the skin to which microemulsion-Carbopol formulations were applied. Conclusion: The results confirm the benefit of TRE solubilization in ME due to its bioavailability from the tested dermal formulations.
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