Wester R C, Patel R, Nacht S, Leyden J, Melendres J, Maibach H
Department of Dermatology, University of California, San Francisco 94143-0989.
J Am Acad Dermatol. 1991 May;24(5 Pt 1):720-6. doi: 10.1016/0190-9622(91)70109-f.
Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled-release styrene-divinylbenzene polymer system. In an in vitro diffusion system, statistically significant (p = 0.01) differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly (p = 0.002) less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings, whereas in vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibacterium acnes (p less than 0.001) and aerobic bacteria (p less than 0.001) and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy.
将含有自由分散药物的外用洗剂中过氧化苯甲酰的皮肤吸收情况与药物包裹于控释苯乙烯 - 二乙烯基苯聚合物系统中的同一洗剂的皮肤吸收情况进行了比较。在体外扩散系统中，发现切除的人体皮肤中过氧化苯甲酰的含量以及经皮吸收存在统计学上的显著差异（p = 0.01）。在体内，从聚合物系统中经恒河猴皮肤吸收的过氧化苯甲酰显著减少（p = 0.002）。这种过氧化苯甲酰向皮肤的控释可改变疗效与皮肤刺激之间存在的剂量关系。相应研究表明，在兔和人的累积刺激性研究中皮肤刺激性降低，而在体内人体抗菌疗效研究中，含有包裹过氧化苯甲酰的制剂的应用显著降低了痤疮丙酸杆菌（p < 0.001）和好氧菌（p < 0.001）的数量以及皮肤脂质中的游离脂肪酸/甘油三酯比率。这些发现支持了这样一种假设，即至少对于这种药物，控释局部给药可在不牺牲疗效的情况下提高安全性。
