Development of timolol maleate ocular insert and evaluation of its anti-glaucoma efficacy in equine eye to maintain performance in a week
Shahla Mirzaeei1 *, Saba Mehrandish2 , Fatemeh Bahrami Faryadras3 , Leila Rezaei4 , Farid Daneshgar5
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Research and Development Department, Rahesh Daru Novin Inc., Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of ophthalmology, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Anterior Segment Department, Fellowship of the Cornea, Kermanshah University of Medical Sciences, Kermanshah, Iran
Abstract: Glaucoma is a chronic condition of the eye that is associated with the degeneration of retinal cells due to various risk factors such as uncontrolled intraocular pressure (IOP). This disease is the second cause of irreversible vision loss in humans; therefore, it should be managed rapidly to prevent further complications. IOP-lowering eye drops like timolol maleate (TIM) are usually prescribed for the treatment of glaucoma. Unfortunately, these forms face some obstacles such as poor patient acceptance due to repetitive administration and rapid removal from the surface of the eye. The present study aimed to design and develop sustained-release inserts for ocular delivery of TIM to achieve higher bioavailability of the drug in the eye.
Methods: TIM was dissolved in different polymeric solutions and TIM-loaded matrices were fabricated. The prepared inserts were characterized for physicochemical properties such as strength, flexibility, weight variation, drug content, morphology, stability, etc. The in vitro release of TIM from the inserts was evaluated and their efficacy in reducing the IOP was investigated in the equine eye. Fourteen glaucomatous horses were selected. A single-dose administration of optimized nanofibrous insert was used as intervention while twice-daily administration of TIM 0.5% eye drops was used as the control. Changes in IOP were evaluated.
Results: The fabricated inserts showed appropriate stability, strength, and flexibility. Suitable morphology with a mean size diameter of 122-174 nm was observed for the nanofibers along with a prolonged in vitro release during 3 days. Similar efficacy was observed for both ocular insert and conventional eye drop formulation (p>0.05). The insert formulation indicated efficacy in lowering the IOP for a 6-days interval.
Conclusion: Despite having similar efficacy as commercial TIM eye drop in lowering the IOP, the ocular insert had the advantage of a sustained release profile which could reduce the required frequency of administration. Accordingly, ocular inserts could be considered suitable for improving TIM ocular delivery and patient acceptance in the treatment of IOP ones in a week.
