Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery System (NODS): rate of clearance of a soluble marker in relation to duration of pharmacological action of pilocarpine.

Abstract

1 A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS) containing pilocarpine nitrate in 12 healthy volunteers. 2 The NODS was radiolabelled with the soluble marker technetium-99m labelled diethylenetriaminepentaacetic acid, to mark the release characteristics of soluble drugs contained within the matrix. 3 The relationship between the precorneal residence time of the marker and the duration of drug effect on intraocular pressure and pupil diameter was monitored.Results obtained following administration of the NODS were compared with those obtained after administration of a 25 RI drop of a 2% w/v pilocarpine nitrate solution.Each formulation was administered to one eye only, the other eye acting as a control. 4 Dissolution of the radiolabel from the NODS in vivo showed considerable intersubject variation with half-times of dissolution ranging from 46 s to 833 s (mean ± s.d. -280 + 217 s), the mean (± s.d.) half-time of clearance of the radiolabel from the NODS and corneal region of interest was 406 ± 214 s whereas the radiolabelled solution had a mean (± s.d.) ocular surface residence time of 2.9 ± 1.5 s. 5 Pupil diameter and intraocular pressure were measured for 5 h post-administration of the NODS and the solution. After both treatments pupil diameter was significantly constricted in the test eye when compared with the control eye (P < 0.001; Student's paired t-test). Pupil diameter was constricted by 52% after administration of the NODS and by 35% after administration of the solution. 6 Intraocular pressure was significantly reduced in the test eye compared with the control eye after administration of the NODS (P < 0.05) but not after administration of the solution. 7 There were no apparent differences in degree of pharmacological action of pilocarpine between subjects with longer half-times of NODS dissolution and those with shorter half-times, indicating that drug diffusion from the matrix was not rate-limiting for the magnitude of the pharmacological effect.

Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model

“…In our assays, exposure to BAC concentrations of 0.02% for 60 minutes demonstrated no toxicity relative to the saline control. Moreover, these durations far exceed those expected in human eyes, for which mean ocular surface residence times have been shown to be as low as 2.9 seconds [ 23 ].…”

Topical drug delivery devices: A review

“…pilocarpine, chloramphenicol and tropicamide (Sesha Rao et al, 2003). This device assured an eight-fold increase in drug bioavailability compared to eye drops in healthy volunteers (Diestelhorst and Krieglstein, 1994;Greaves et al, 1992;Saettone and Salminen, 1995). A small clinical trial with twelve volunteers revealed intense miosis in all test subjects as a side effect (Greaves et al, 1992).…”

“…This device assured an eight-fold increase in drug bioavailability compared to eye drops in healthy volunteers (Diestelhorst and Krieglstein, 1994;Greaves et al, 1992;Saettone and Salminen, 1995). A small clinical trial with twelve volunteers revealed intense miosis in all test subjects as a side effect (Greaves et al, 1992). In a larger study with twenty-nine volunteers, there were some problems with the detachment of the NODS ® from its applicator (Diestelhorst and Krieglstein, 1994).…”

Promising therapeutic drug delivery systems for glaucoma: a comprehensive review

“…NODS is manufactured using water-soluble polyvinyl alcohol (PVA). Greaves and colleagues 22 used radiolabeled NODS loaded with pilocarpine nitrate, to evaluate the pharmacokinetics and bioavailability in human subjects. They found an eightfold precorneal bioavailability and higher compliance among the test subjects pilocarpine NODS as compared with a 2% w/v pilocarpine nitrate solution.…”