Dataset Information

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

ABSTRACT:

Purpose

We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo.

Methods

Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ?40 and 20??m for timolol and brimonidine compartments, respectively. In vitro release kinetics were measured in pH- and temperature-controlled fluid chambers. Empty or drug-loaded devices were implanted intracamerally in normotensive rabbits for up to 13 weeks with weekly measurements of IOP. For ocular concentrations, rabbits were euthanized at 4, 8, or 13 weeks, aqueous fluid was collected, and ocular tissues were dissected. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry.

Results

In vitro studies show zero-order release kinetics for both timolol (1.75??g/day) and brimonidine (0.48??g/day) for up to 60 days. In rabbit eyes, the device achieved an average aqueous fluid concentration of 98.1?±?68.3?ng/mL for timolol and 5.5?±?3.6?ng/mL for brimonidine. Over 13 weeks, the drug-loaded co-delivery device resulted in a statistically significant cumulative reduction in IOP compared to untreated eyes (P?ConclusionsThe co-delivery device demonstrated a zero-order release profile in vitro for 2 hypotensive agents over 60 days. In vivo, the device led to significant cumulative IOP reduction of 3.4?±?1.6?mmHg over 13 weeks. Acceptable ocular tolerance was seen, and systemic drug levels were unmeasurable.

SUBMITTER: Samy KE

PROVIDER: S-EPMC6450452 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

Samy Karen E KE Cao Yiqi Y Kim Jean J Konichi da Silva Nina Rosa NR Phone Audrey A Bloomer Michele M MM Bhisitkul Robert B RB Desai Tejal A TA

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 20190107 2

<h4>Purpose</h4>We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo.<h4>Methods</h4>Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 μm for timolol and brimonidine compartments, respectively. In vitro release kinetic ...[more]

PMID: 30615539

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Project description:OBJECTIVE:To evaluate the additive intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%/timolol 0.5% compared with timolol 0.5% at peak and trough effect when used as therapy adjunctive to latanoprost 0.005% in patients with glaucoma or ocular hypertension who require additional IOP lowering. METHODS:In this prospective, randomized, multicenter, investigator-masked, parallel-group study, patients were treated with latanoprost monotherapy for at least four weeks prior to baseline. At baseline on latanoprost, patients with IOP ?21 mmHg in at least one eye were randomized to twice-daily fixed brimonidine-timolol (n = 102) or timolol (n = 102), each adjunctive to latanoprost for 12 weeks. IOP was measured at 8 am and 10 am at baseline, week 6, and week 12 and evaluated in the per protocol population. The primary efficacy endpoint was peak IOP lowering at 10 am, week 12. Safety measures included adverse events. RESULTS:Baseline mean IOP was similar at 10 am in the treatment groups (brimonidine-timolol 23.4 mmHg; timolol 23.0 mmHg). The mean additional reduction from latanoprost-treated baseline IOP was 8.3 mmHg (35.5%) with fixed brimonidine-timolol and 6.2 mmHg (27.0%) with timolol at 10 am, week 12 (P < 0.001). Patients treated with fixed brimonidine-timolol adjunctive to latanoprost were significantly more likely than patients treated with adjunctive timolol to achieve an IOP <18 mmHg (P = 0.028) and a ?20% reduction in IOP from baseline (P = 0.047) at both 8 am and 10 am in week 12. Adverse events occurred in 14.7% of fixed brimonidine-timolol patients and 12.7% of timolol patients. Biomicroscopy findings were similar between the treatment groups after 12 weeks of treatment. CONCLUSION:Fixed-combination brimonidine-timolol reduced IOP significantly more effectively than timolol when used as adjunctive therapy to latanoprost in patients with glaucoma and ocular hypertension. Both fixed brimonidine-timolol and timolol were well tolerated as agents adjunctive to latanoprost.

Dataset Information

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

Purpose

Methods

Results

Publications

Co-Delivery of Timolol and Brimonidine with a Polymer Thin-Film Intraocular Device.

Similar Datasets

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