Fiala Sarah, Brown Marc B, Jones Stuart A
Pharmaceutical Science Division, King's College London, 150 Stamford Street, London SE1 9NH, UK.
J Pharm Pharmacol. 2008 Dec;60(12):1615-23. doi: 10.1211/jpp/60.12.0007.
Few studies have assessed the impact of binary systems on the fundamental mathematical models that describe drug permeation. The aim of this work was to determine the influence of varying the proportions of prilocaine and lidocaine in a binary saturated solution on mass transfer across synthetic membranes. Infinite-dose permeation studies were performed using Franz diffusion cells with either regenerated cellulose or silicone membranes, and partition coefficients were determined by drug loss over 24 h. There was a linear relationship between the flux of prilocaine and lidocaine through regenerated cellulose membrane (R(2) >or= 0.985, n = 5) and their normalised ratio in solution. This linear model was also applicable for the permeation of prilocaine through silicone membrane (R(2) = 0.991, n = 5), as its partition coefficient was independent of the drug ratio (15.84 +/- 1.41). However, the partition coefficient of lidocaine increased from 27.22 +/- 1.68 to 47.03 +/- 3.32 as the ratio of prilocaine increased and this resulted in a non-linear relationship between permeation and drug ratio. Irrespective of the membrane used, the permeation of one drug from a binary system was hindered by the presence of the second, which could be attributed to a reduction in available membrane diffusion volume.
很少有研究评估二元体系对描述药物渗透的基本数学模型的影响。本研究的目的是确定在二元饱和溶液中改变丙胺卡因和利多卡因的比例对通过合成膜的传质的影响。使用带有再生纤维素或硅酮膜的Franz扩散池进行无限剂量渗透研究,并通过24小时内药物损失来确定分配系数。丙胺卡因和利多卡因通过再生纤维素膜的通量与其在溶液中的归一化比例之间存在线性关系(R(2)≥0.985,n = 5)。该线性模型也适用于丙胺卡因通过硅酮膜的渗透(R(2) = 0.991,n = 5),因为其分配系数与药物比例无关(15.84±1.41)。然而,随着丙胺卡因比例的增加,利多卡因的分配系数从27.22±1.68增加到47.03±3.32,这导致渗透与药物比例之间呈非线性关系。无论使用何种膜,二元体系中一种药物的渗透都会受到另一种药物的阻碍,这可能归因于可用膜扩散体积的减少。