Pregabalin Microemulsion Once Daily Eye Drops for the Management of Glaucoma
Monica M Jablonski PhD FARVO University of Tennessee Health Science Center, Ophthalmology
Co-authors: Doaa N Maria PhD Mohamed M Ibrahim
Purpose: Our study was designed to develop a novel pregabalin-loaded topical ophthalmic microemulsion-based formulation as a once-daily IOP-lowering drop. Methods: We engineered a mucoadhesive W/O/W microemulsion containing pregabalin and characterized it using multiple in-vitro and in-vivo evaluations including: particle size, zeta potential, viscosity and mucoadhesion, drug release, corneal permeability, cytotoxicity, in-vivo safety and efficacy studies. Results: Our microemulsion was engineered using highly biocompatible components with in-situ gelling properties that improve viscosity and bioadhesion, enhance corneal penetration and provide continuous drug release for 24h. Because our microemulsion has miniscule particle size (< 20nm), it is transparent and does not blur vision. Our formulation is safe to the eye, as demonstrated with MTT assay and slit-lamp biomicroscopic exams, which showed that there is no any sign of irritation. Also, our formulation markedly enhances pregabalin efficacy. Using Dutch belted rabbits, we effectively demonstrate that a single drop of our microemulsion can induce >40% reduction in IOP that returns to baseline at 34h after dosing. In the absence of our microemulsion, the same drug produced only 29% IOP reduction that returned to baseline after 10h. Conclusions: We have engineered novel topical ophthalmic formulation that supported once daily dosing of pregabalin as a novel IOP-lowering therapy. Our formulation greatly improves pregabalin IOP-lowering efficacy both in terms of amplitude and duration of response, which is supported by improved mucoadhesion, increased corneal permeability, penetration enhancing ability and sustained release behavior. If replicated in prospective clinical trials, our formulation could revolutionize glaucoma therapy. Acknowledgements: The authors thank Dr. J. Bumgardner (Department of Biomedical Engineering, The University of Memphis) for the use of his viscometer.
This study was supported by an unrestricted grant from Research to Prevent Blindness (RPB; New York, NY), the University of Tennessee Research Foundation (UTRF), the UTHSC Neuroscience Institute, and the UTHSC Collaborative Research Network (CORNET).
