Effect of topically applied pilocarpine on tear film pH

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.