Absorption of solvent-deposited weak electrolytes and their salts through human skin in vitro
Absorption of solvent-deposited weak electrolytes and their salts through human skin in vitro
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溶剂沉积的弱电解质及其盐通过人体皮肤的体外吸收
DOI：
10.1016/j.ijpharm.2022.121753
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发表时间：
2022
影响因子：
5.8
通讯作者：
Kasting, Gerald B.
中科院分区：
文献类型：
--
作者：
Miller, Matthew A.;Kasting, Gerald B.
分别在11 - 11，000 nmol/cm 2和1.93-1930 nmol/cm 2的放射性标记剂量溶剂沉积后0 - 72 h，测定了弱酸（苯甲酸）和弱碱（普萘洛尔）在电离的不同阶段通过体外人皮肤的渗透。对于每种化合物检测的20种组合，在72小时内渗透到受体液中的平均渗透率范围为苯甲酸剂量的1.5%至40.7%，普萘洛尔剂量的1.3%至35.5%。除了最低剂量外，所有剂量的渗透均随剂量溶液中非离子化渗透物分数的增加而增加。一般来说，这种趋势随着剂量的增加而增强。普萘洛尔的放射性回收率平均为94.3 ± 5.5%，与电离状态和剂量无关。苯甲酸的放射性回收率范围为40%至> 100%，随非离子化部分和剂量增加而增加。这些作用可以定性地解释为离子化物质通过角质层的低渗透性、游离苯甲酸的挥发性和角质层沉积区域的缓冲容量为10-20 nmol/cm 2。
Permeation of a weak acid (benzoic acid) and a weak base (propranolol) in various stages of ionization through human skin in vitro was measured from 0 to 72 h following solvent deposition of radiolabeled doses ranging from 11 to 11,000 nmol/cm2and 1.93–1930 nmol/cm2, respectively. For the twenty combinations tested for each compound, mean permeation into the receptor fluid over 72 h ranged from 1.5 to 40.7 percent of dose for benzoic acid and 1.3–35.5 percent of dose for propranolol. For all but the lowest doses, permeation increased with increasing fraction of nonionized permeant in the dose solution. Generally, this trend became stronger as the dose increased. Recovery of radioactivity averaged 94.3 ± 5.5% for propranolol and was independent of ionization state and dose. Recovery of radioactivity for benzoic acid ranged from 40 to >100%, increasing with fraction nonionized and with dose. These effects can be qualitatively explained in terms of the low permeability of ionized species through stratum corneum, the volatility of free benzoic acid, and a buffer capacity of the stratum corneum deposition region on the order of 10–20 nmol/cm2.