Freedman K A, Klein J W, Crosson C E
Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock.
Curr Eye Res. 1993 Jul;12(7):641-7. doi: 10.3109/02713689309001843.
Cyclodextrins have been used to improve drug solubility, stability and absorption for oral and parenteral administration. However, their potential for improving ocular drug delivery has received little attention. To evaluate the ability of hydroxypropyl-beta-cyclodextrins to improve ophthalmic drug bioavailability following topical administration, the miotic effect of topical solutions of pilocarpine was studied in New Zealand White rabbits. Pilocarpine varying in dose from 5 to 500 micrograms in the presence or absence of 5% cyclodextrin was administered (50 microliters) topically and the change in pupil diameter determined. These results demonstrated that pilocarpine alone or in the presence of cyclodextrin produces a dose-related reduction in pupil diameter. The addition of cyclodextrins produced a significant left-shift in the dose response curve, with an ED50 of 64 micrograms and 19 micrograms for pilocarpine and pilocarpine/5% cyclodextrin solutions, respectively. Studies in which the concentration of cyclodextrin was varied revealed that a one-to-one molar ratio of pilocarpine to cyclodextrin was sufficient to provide maximum increase in pilocarpine bioavailability. Electrophysiology and scanning electron microscopic studies demonstrated that cyclodextrin does not disrupt the normal ion transport currents, barrier properties or surface features of the corneal epithelium. Viscosity measurements indicated that difference in the viscosity of pilocarpine and pilocarpine/cyclodextrin solutions cannot account for increased bioavailability of pilocarpine. These data support the idea that the addition of cyclodextrin significantly improves the ocular bioavailability of pilocarpine. This enhanced bioavailability of pilocarpine does not appear to be due to a mechanism destructive to the epithelium or to an increase in vehicle viscosity.
环糊精已被用于提高药物的溶解度、稳定性以及口服和肠胃外给药的吸收。然而，它们在改善眼部药物递送方面的潜力却很少受到关注。为了评估羟丙基-β-环糊精在局部给药后改善眼科药物生物利用度的能力，研究了毛果芸香碱局部溶液在新西兰白兔中的缩瞳作用。分别给予含或不含5%环糊精、剂量为5至500微克的毛果芸香碱（50微升）进行局部给药，并测定瞳孔直径的变化。这些结果表明，单独使用毛果芸香碱或在环糊精存在的情况下，都会使瞳孔直径产生剂量相关的减小。加入环糊精后，剂量反应曲线显著左移，毛果芸香碱溶液和毛果芸香碱/5%环糊精溶液的半数有效剂量（ED50）分别为64微克和19微克。改变环糊精浓度的研究表明，毛果芸香碱与环糊精的摩尔比为1:1时，足以使毛果芸香碱的生物利用度得到最大程度的提高。电生理学和扫描电子显微镜研究表明，环糊精不会破坏角膜上皮的正常离子传输电流、屏障特性或表面特征。粘度测量表明，毛果芸香碱溶液和毛果芸香碱/环糊精溶液的粘度差异不能解释毛果芸香碱生物利用度增加的原因。这些数据支持了环糊精的加入能显著提高毛果芸香碱眼部生物利用度这一观点。毛果芸香碱生物利用度提高似乎并非由于对上皮有破坏作用的机制或载体粘度增加所致。
