Okumura M, Nakamori Y, Yoshida Y, Niwa H, Sugibayashi K, Morimoto Y
Omiya Research Laboratory, Nikken Chemicals Co., Ltd, Saitama, Japan.
Drug Des Deliv. 1990 Jun;6(2):137-48.
The skin permeation enhancement of papaverine hydrochloride by free fatty acids (C3-C12), monoglycerides (side chains C5-C12) and caprylic acid (C8) esters was evaluated using the excised hairless rat skin. Enhancement was marked in the case of glyceryl monocaprylate; the cumulative amount of papaverine that permeated through skin over 28 hours from an aqueous suspension was 29.7 mg/cm2 with, and 26.9 micrograms/cm2 without glyceryl monocaprylate. The mechanism of enhancement was studied by measuring the effect the enhancers had on the diffusion and partition parameters of papaverine. Free fatty acids mainly affected the drug's diffusion, and monoglycerides mainly affected the drug's partition. For monoglyceride enhancers, a good linear relationship between the flux of papaverine and the amount of enhancer in skin was established. n-Octanol-water partition coefficients (log Pcal) of the enhancers were selected as indicators of their physicochemical properties, and related to their penetration-enhancing abilities. A parabolic relationship was found between the log of the flux of papaverine and log Pcal, for all types of enhancers. The relationship may be a good indicator in predicting enhancing effects.
使用切除的无毛大鼠皮肤评估了游离脂肪酸（C3 - C12）、甘油单酯（侧链C5 - C12）和辛酸（C8）酯对盐酸罂粟碱皮肤渗透的增强作用。单辛酸甘油酯的增强作用显著；从水悬浮液中，28小时内透过皮肤的罂粟碱累积量，有单辛酸甘油酯时为29.7mg/cm²，无单辛酸甘油酯时为26.9μg/cm²。通过测量增强剂对罂粟碱扩散和分配参数的影响来研究增强机制。游离脂肪酸主要影响药物的扩散，甘油单酯主要影响药物的分配。对于甘油单酯增强剂，建立了罂粟碱通量与皮肤中增强剂含量之间良好的线性关系。选择增强剂的正辛醇 - 水分配系数（log Pcal）作为其物理化学性质的指标，并将其与渗透增强能力相关联。对于所有类型的增强剂，发现罂粟碱通量的对数与log Pcal之间存在抛物线关系。这种关系可能是预测增强效果的良好指标。
