Delhi Institute of Pharmaceutical Sciences and Research, Pusph Vihar, Sector-3, M.B. Road, New Delhi 110017, India.
Saudi Pharm J. 2011 Jul;19(3):165-70. doi: 10.1016/j.jsps.2011.03.007. Epub 2011 Mar 31.
The purpose of the present study was to evaluate the transport of ascorbic acid, a water soluble molecule, through a predominantly lipophilic cornea. Thus in-vitro permeation of ascorbic acid from aqueous drops through freshly excised mammalian cornea was studied. Aqueous isotonic ophthalmic solutions of ascorbic acid of different concentrations (0.125% w/v to 2% w/v) (pH 5.4) were made. Further 1.0% w/v or 0.5% w/v ascorbic acid solution containing NaCl or dextrose as tonicity modifiers or Na(+)K(+)-ATPase inhibitors were also made. Permeation characteristics of drug were evaluated by putting 1 ml formulation on freshly excised cornea fixed between donor and receptor compartments of an all-glass modified Franz diffusion cell and measuring the drug permeated in the receptor by spectrophotometry at 265 nm, after 120 min. Statistical analysis was done by one-way analysis of variance (ANOVA) followed by Dunnett's test or paired t-test. Increase in drug concentration in the formulation resulted in an increase in the quantity permeated but after a certain level increase in permeation with increase in concentration was minimal. Aqueous drops made isotonic with dextrose showed decreased permeation through paired cornea compared with aqueous drops made isotonic with NaCl from 1% w/v ascorbic acid solution suggesting likely involvement of Na(+) co-transporter but there was decreased permeation through 0.5% w/v ascorbic acid solution made isotonic with NaCl as compared to solution made isotonic with dextrose. Further aqueous drops containing Na(+)K(+)-ATPase inhibitor {MAG-Mono Ammonium Glycyrrhizinate (25 μmol)} showed decreased corneal permeation from 0.5% w/v ascorbic acid solution but there was not significant decrease from 1% ascorbic acid solution since MAG is a competitive inhibitor of ascorbic acid. Aqueous drops containing Na(+)K(+)-ATPase inhibitor {MAG (50 μmol) or Ouabain (1 mmol)} showed decreased corneal permeation of ascorbic acid compared with control from 1% ascorbic acid solution confirming the involvement of Na(+) co-transporter.
本研究旨在评估水溶性分子抗坏血酸通过主要亲脂性角膜的转运情况。因此，研究了不同浓度（0.125% w/v 至 2% w/v）（pH 5.4）的抗坏血酸水溶液滴眼剂通过新鲜离体哺乳动物角膜的体外渗透情况。还制备了含有 NaCl 或葡萄糖作为等渗调节剂或 Na(+)K(+)-ATP 酶抑制剂的 1.0% w/v 或 0.5% w/v 抗坏血酸溶液。将 1 ml 制剂置于新鲜离体角膜上，将其固定在全玻璃改良 Franz 扩散池的供体和受体隔室之间，通过分光光度法在 265nm 处测量受体中渗透的药物，120 分钟后。通过单向方差分析（ANOVA）进行统计学分析，然后进行 Dunnett 检验或配对 t 检验。制剂中药物浓度的增加导致渗透量增加，但在一定水平后，随着浓度的增加，渗透增加最小。与用 NaCl 制成等渗的水溶液相比，用葡萄糖制成等渗的水溶液滴眼剂使 1% w/v 抗坏血酸溶液透过配对角膜的渗透减少，这表明可能涉及 Na(+)协同转运体，但与用葡萄糖制成等渗的溶液相比，用 NaCl 制成等渗的 0.5% w/v 抗坏血酸溶液的渗透减少。进一步含有 Na(+)K(+)-ATP 酶抑制剂 {MAG-单铵甘草酸盐（25μmol）}的水溶液滴眼剂从 0.5% w/v 抗坏血酸溶液中显示出角膜渗透减少，但从 1%抗坏血酸溶液中没有显著减少，因为 MAG 是抗坏血酸的竞争性抑制剂。含有 Na(+)K(+)-ATP 酶抑制剂 {MAG（50μmol）或哇巴因（1mmol）}的水溶液滴眼剂与对照相比，从 1%抗坏血酸溶液中显示出抗坏血酸的角膜渗透减少，证实了 Na(+)协同转运体的参与。
