Goskonda V R, Hill R A, Khan M A, Reddy I K
Division of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe 71209, USA.
Pharm Dev Technol. 2000;5(3):409-16. doi: 10.1081/pdt-100100557.
The purpose of this study was to investigate the corneal permeability of phenylephrone chemical delivery systems (CDS) across isolated cornea and to evaluate the utility of the SIRC cell line (epithelial cells originating from rabbit cornea) as an in vitro model for predicting the ocular permeability. The effect of benzalkonium chloride (BAC) on the drug permeability through SIRC cell layers was also studied. The transport of phenylephrone CDS across the isolated cornea of the albino rabbit was measured at various pH values using a two-chamber glass diffusion cell, and the results were compared with the reported permeability values across SIRC cells of rabbit origin. Corneal membranes showed lower flux values for compounds, especially for hydrophilic compounds, than the SIRC cell line. A significant correlation was observed between the permeability coefficients through corneal membranes and SIRC cells. When the pH of the transport medium was increased, the permeability coefficients increased and lag times decreased in both in vitro models. Furthermore, both in vitro models showed significant correlation between permeability coefficients and lipophilicities of the drugs. The three esters, having higher lipophilic characteristics, showed higher permeability than phenylephrine HCl. The phenylacetyl ester of phenylephrone showed a three-fold increase in penetration across SIRC cell layers in the presence of 0.01% BAC. These results suggest that the use of SIRC cell layers can reasonably predict the permeability of ophthalmic drugs across corneal membranes.
本研究的目的是研究去氧肾上腺素化学传递系统（CDS）在离体角膜中的通透性，并评估SIRC细胞系（源自兔角膜的上皮细胞）作为预测眼部通透性的体外模型的实用性。还研究了苯扎氯铵（BAC）对药物透过SIRC细胞层的通透性的影响。使用两室玻璃扩散池在不同pH值下测量去氧肾上腺素CDS在白化兔离体角膜中的转运，并将结果与报道的兔源SIRC细胞的通透性值进行比较。与SIRC细胞系相比，角膜膜对化合物的通量值较低，尤其是亲水性化合物。观察到通过角膜膜和SIRC细胞的渗透系数之间存在显著相关性。当转运介质的pH值升高时，两种体外模型的渗透系数均增加，滞后时间均减少。此外，两种体外模型均显示渗透系数与药物亲脂性之间存在显著相关性。三种具有较高亲脂性特征的酯，其通透性高于盐酸去氧肾上腺素。在0.01% BAC存在下，去氧肾上腺素的苯乙酰酯在穿过SIRC细胞层时的渗透率增加了三倍。这些结果表明，使用SIRC细胞层可以合理预测眼科药物在角膜膜中的通透性。
