Sarango-Granda Paulo, Espinoza Lupe Carolina, Díaz-Garrido Natalia, Alvarado Helen, Rodríguez-Lagunas María J, Baldomá Laura, Calpena Ana
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain.
Pharmaceutics. 2022 May 7;14(5):1011. doi: 10.3390/pharmaceutics14051011.
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.
阿普米拉斯（APR）的水溶性差是该药物透过皮肤屏障的主要障碍。本研究的目的是评估APR在富含渗透促进剂的不同溶液中对人皮肤离体样本的渗透性，并另外评估其体内耐受性。为此，研发了含5%促进剂的APR溶液，并评估该药物穿透人腹部皮肤样本的能力；评估的参数包括渗透率系数、累积渗透量和流量；同样，也评估了溶液的体外和体内耐受性。所得结果表明，与其他评估的促进剂相比，含角鲨烯作为促进剂的溶液提高了APR的渗透率；同样，在体外HaCaT细胞实验中，这些促进剂无毒，在评估的不同稀释度下细胞活力均大于80%。在用呈现最佳结果的溶液（APR-角鲨烯溶液）进行的体内试验中，观察到在对大鼠背部区域进行应用后的比色和组织学评估后，该溶液不会引起皮肤刺激或红斑。在开发局部用制剂的情况下，角鲨烯成为提高药物渗透率的极佳候选物；此外，在体内试验中证实，这种渗透促进剂与皮肤接触时既无毒也无刺激性。
