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，也是光老化金标准治疗方案的组成成分。另有研究报道，高浓度的维A酸制剂可作为浅表化学剥脱剂，且当时针对其皮肤渗透行为的相关考量较少。本研究旨在考察药物浓度与临床常用基质对维A酸皮肤渗透性能的影响。本研究采用搭载猪耳皮肤（porcine ear skin）的Franz扩散池（Franz diffusion cells）开展体外透皮渗透试验，接收池（receptor compartment）内填充10%甲醇水溶液。供体池（donor compartment）中分别加入含0.25%、1%及5%维A酸的乳膏或水醇分散体（hydroalcoholic dispersion）制剂，持续孵育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。试验结果显示，两种基质的维A酸最大蓄积量均检测于角质层（stratum corneum），且三个浓度组间的差异具有统计学意义。其中水醇分散体的透皮效果更优；即便在表皮深层，也可检测到可观量的维A酸。以皮肤中维A酸的百分比留存量为评价指标时，含0.25%维A酸的制剂表现更佳。最终证实，维A酸的皮肤渗透行为受制剂基质与药物浓度的共同影响。