Reduction of intraocular pressure using timolol orally dissolving strips in the treatment of induced primary open-angle glaucoma in rabbits

J Pharm Pharmacol. 2020 May;72(5):682-698. doi: 10.1111/jphp.13239. Epub 2020 Mar 14.

Abstract

Objective: To enhance bioavailability of timolol (TML) and utilize alternatives for traditional eye drops for more patient compliance, this study was aiming to develop biodegradable orally dissolving strips (ODSs) of TML for treatment of primary open-angle glaucoma (POAG).

Methods: Novel ODSs of TML were formulated and optimized using solvent casting method according to full factorial design (31 .22 ). TML ODSs were characterized with respect to many parameters. In-vivo test was carried out using four groups of 24 New Zealand albino rabbits. POAG was induced by subconjunctival treatment of betamethasone. Histopathological examination and oxidative stress markers assay were carried out.

Key findings: The optimized formula (F9) exhibited a remarkably 15-s disintegration time and 96% dissolution rate after 10 min. The results revealed a potent significant inhibitory effect of the optimized TML ODS to reduce IOP in induced rabbits in comparison with control rabbits and TML eye drops-treated rabbits. The formula showed also high activity against oxidative stress and absence of histopathological changes in iridocorneal angle and cornea.

Conclusion: The ODSs could be a promising alternative delivery system for eye drops with more compliance to enhance delivery and therapeutic activity of TML in treatment of POAG.

Keywords: fast release; intraocular pressure; orally dissolving strips; primary open-angle glaucoma; timolol.

MeSH terms

  • Administration, Oral
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacokinetics*
  • Antihypertensive Agents / therapeutic use
  • Biological Availability
  • Drug Compounding
  • Drug Delivery Systems
  • Drug Liberation
  • Drug Stability
  • Glaucoma, Open-Angle / drug therapy*
  • Glaucoma, Open-Angle / metabolism*
  • Glaucoma, Open-Angle / pathology
  • Glaucoma, Open-Angle / physiopathology
  • In Vitro Techniques
  • Intraocular Pressure / drug effects*
  • Oxidative Stress / drug effects
  • Polymers / pharmacokinetics
  • Rabbits
  • Timolol / administration & dosage
  • Timolol / pharmacokinetics*
  • Timolol / therapeutic use

Substances

  • Antihypertensive Agents
  • Polymers
  • Timolol