Longwell A, Birss S, Keller N, Moore D
J Pharm Sci. 1976 Nov;65(11):1654-7. doi: 10.1002/jps.2600651123.
Changes in tear film pH were observed during the 1st hr after instillation of pilocarpine in various dosage forms to the rabbit eye. In anesthetized rabbits, with periodic blinking induced electrically, commercial formulations of pilocarpine salts applied as drops or a spray acutely lowered tear film pH by 1.1-1.6 pH units. The pH remained below pretreatment levels for 45-greater than 60 min after instillation. Pilocarpine base, administered continuously at the rates of 20 or 80 mug/hr from ocular therapeutic systems, had little or no effect on tear film pH in this same animal preparation. The reduction in tear film pH produced by pilocarpine eyedrops or spray solution is attributable to the acid pH and buffer capacity of these solutions. Delivery of pilocarpine base without pH change was achieved with ocular therapeutic systems, because the drug (pKa = 7.07) was delivered free, or virtually so, of excipients. These observed differences in tear film pH after application may partially explain the four- to eightfold reduction in total effective pilocarpine dose with ocular therapeutic systems compared to eyedrops or spray, since the cornea is less permeable to ionized than to unionized molecules.
在向兔眼滴入各种剂型的毛果芸香碱后的第1小时内，观察泪膜pH值的变化。在麻醉的兔子中，通过电诱导使其周期性眨眼，以滴剂或喷雾形式应用的毛果芸香碱盐的市售制剂可使泪膜pH值急性降低1.1 - 1.6个pH单位。滴入后，pH值在45 - 超过60分钟内保持低于预处理水平。从眼部治疗系统以20或80微克/小时的速率持续给药毛果芸香碱碱，在相同的动物制剂中对泪膜pH值几乎没有影响。毛果芸香碱滴眼液或喷雾溶液引起的泪膜pH值降低归因于这些溶液的酸性pH值和缓冲能力。眼部治疗系统实现了毛果芸香碱碱的无pH值变化递送，因为药物（pKa = 7.07）是以游离或几乎游离于辅料的形式递送的。与滴眼液或喷雾相比，眼部治疗系统应用后观察到的泪膜pH值差异可能部分解释了毛果芸香碱总有效剂量降低四至八倍的原因，因为角膜对离子化分子的通透性低于对非离子化分子的通透性。
