Tretinoin-based formulations - influence of concentration and vehicles on skin penetration

Tretinoin is used in the management of acne and it is part of a gold standard treatment for photoaging. It has also been reported as an agent for superficial chemical peeling in highly concentrated formulations with few considerations about skin penetration. The aim of this study was to evaluate the influence of drug concentration and vehicles currently used on skin penetration of tretinoin. In vitro permeation tests were carried out using Franz diffusion cells fitted with porcine ear skin and 10% aqueous methanol in the receptor compartment. Formulations studied, cream or hydroalcoholic dispersion, containing 0.25%, 1% and 5% of tretinoin were placed in the donor compartment for six hours. Tretinoin concentration in skin layers was measured by high performance liquid chromatography. The largest amount of tretinoin from both vehicles was detected in stratum corneum with significant differences among the three concentrations. The hydroalcoholic dispersion was the best vehicle. Significant amounts of tretinoin were found even in deep layers of epidermis. The formulation with 0.25% tretinoin showed better results when considered the amount of tretinoin on skin in terms of percentage. Finally, skin penetration of tretinoin was influenced by vehicle and concentration of this drug used in formulation.维A酸（Tretinoin）常用于痤疮的临床管理，亦是光老化金标准治疗方案的组成部分。另有研究报道，高浓度配方中的维A酸可作为浅表化学剥脱剂，且无需过多考量皮肤渗透性相关问题。本研究旨在考察药物浓度与当前常用制剂基质对维A酸皮肤渗透性的影响。本实验采用猪耳皮肤作为透皮模型，搭配Franz扩散池（Franz diffusion cells）开展体外透皮试验，受体室填充10%甲醇水溶液。将分别含有0.25%、1%及5%维A酸的乳膏或水醇分散体作为供试液，置于供体室中孵育6小时。采用高效液相色谱法（high performance liquid chromatography）测定皮肤各层中的维A酸浓度。实验结果显示：两种制剂基质的维A酸均在角质层（stratum corneum）中检出量最高，且三个浓度组间差异具有统计学意义；水醇分散体的透皮效果优于乳膏；即便在表皮深层组织中，也可检测到可观含量的维A酸；以皮肤中维A酸的百分含量为评价指标时，含0.25%维A酸的配方表现最优。综上，维A酸的皮肤渗透性受制剂基质与药物浓度双重影响。