Calatayud-Pascual María Aracely, Sebastian-Morelló María, Balaguer-Fernández Cristina, Delgado-Charro M Begoña, López-Castellano Alicia, Merino Virginia
Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Spain.
Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Pharmaceutics. 2018 Dec 7;10(4):265. doi: 10.3390/pharmaceutics10040265.
The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm² were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm² were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.
本研究的目的是在体外评估经皮给予普萘洛尔的可能性,并以普萘洛尔作为模型化合物,评估皮肤药代动力学(DPK)方法在评估药物透过角质层转运方面的实用性。测试了四种化学增强剂(癸烯酸和油酸、月桂氮卓酮和R-(+)-柠檬烯)以及两种电流密度(0.25和0.5 mA/cm²)下的离子导入。结果证明,R-(+)-柠檬烯以及0.5 mA/cm²的离子导入在增加普萘洛尔经皮通量方面最为有效,两者均使普萘洛尔的原始经皮通量增加了一倍。已证明离子导入优于化学增强剂,因为它能更快地递送药物。DPK方法足够灵敏,能够检测到载体对普萘洛尔皮肤渗透的细微影响。这些实验的持续时间较短,且有能力提供关于载体与皮肤之间分配以及透过皮肤扩散系数的机制信息,使其成为一种实用且可能具有深刻见解的方法,用于量化并最终优化局部生物利用度。