In Vitro and In-Eye Comparison of Commercial Pilocarpine Ophthalmic Solution and an Optimized, Reformulated Pilocarpine for Presbyopia Treatment

Abstract

Introduction: Pilocarpine hydrochloride (pilo) ophthalmic solution has traditionally been used for the treatment of glaucoma, with opportunities to improve the tolerability profile experienced by patients. Pilocarpine hydrochloride ophthalmic solution 1.25% (Vuity TM , Allergan, an AbbVie company) was approved in late 2021 for the treatment of adults with presbyopia. This publication describes the properties of the optimized, proprietary vehicle of this new ophthalmic solution developed with the aim of improving tolerability upon instillation. Methods: An in vitro method determined the time required for the pH of pilo 1.25% in the proprietary vehicle (Optimized Formulation) and a commercially available 1% pilo ophthalmic solution (Generic Formulation) to equilibrate with the pH of simulated tear fluid (STF). In a pilot study, five of the six screened participants received one drop of the Optimized Formulation in one eye and Generic Formulation in the other. Ocular discomfort and vision blur were evaluated for each eye just prior to and at multiple times after drop instillation using visual analog scales (VAS), and adverse events were assessed. Results: The in vitro method showed that the Optimized Formulation achieved faster pH equilibration than the Generic Formulation. The pilot study revealed that the Optimized Formulation demonstrated less ocular discomfort, vision blur, and adverse events compared to the Generic. Conclusion:The in vitro and pilot study of the Optimized Formulation indicated that it rapidly equilibrates to the physiologic pH of the tear film, providing greater comfort and tolerability while also minimizing vision blur. Overall, the proprietary vehicle is expected to improve comfort, result in less vision blur, and provide a well-tolerated alternative method to deliver pilo for the treatment of presbyopia when compared to what is commercially available.

Pilocarpine Hydrochloride Ophthalmic Solution 1.25%: An Innovative Prescription Eye Drop for the Treatment of Presbyopia

“…24 However, anatomical and physiological barriers to effective delivery have presented a challenge. 17 Furthermore, their use has been historically associated with side effects such as ocular discomfort, redness, inflammation, headache and vision blur. 17,24,29,30 The current literature thus highlights an unmet need in the presbyopia treatment landscape.…”

“…The product was designed specifically for the treatment of presbyopia (based on the unmet need for a non-invasive pharmacological eye drop) and reformulated to improve bioavailability and tolerability. 13,17 A low pH (~4) is required to stabilize pilocarpine in generic ophthalmic solution, due to a high susceptibility of pilocarpine to hydrolysis at physiological pH (~7). 17,36 However, pilocarpine is protonated (or ionized) at low pH, leading to poor transcorneal permeation and, consequently, limited bioavailability at target tissues.…”

“…13,17 A low pH (~4) is required to stabilize pilocarpine in generic ophthalmic solution, due to a high susceptibility of pilocarpine to hydrolysis at physiological pH (~7). 17,36 However, pilocarpine is protonated (or ionized) at low pH, leading to poor transcorneal permeation and, consequently, limited bioavailability at target tissues. 17,37 The low pH of generic pilocarpine ophthalmic solution may also cause some of the adverse effects experienced by patients with glaucoma.…”

“…17,36 However, pilocarpine is protonated (or ionized) at low pH, leading to poor transcorneal permeation and, consequently, limited bioavailability at target tissues. 17,37 The low pH of generic pilocarpine ophthalmic solution may also cause some of the adverse effects experienced by patients with glaucoma. 36 With this in mind, a reengineered ophthalmic solution was designed to equilibrate rapidly to the pH of the ocular surface to improve bioavailability and reduce side effects such as ocular discomfort and vision blur.…”

“…In vitro studies and a phase I clinical trial evaluated the properties of the pHast™ technology-based formulation of pilocarpine HCl ophthalmic solution 1.25%, compared with a generic formulation of pilocarpine HCl 1.0% commercially available for the treatment of glaucoma. 17 The first in vitro study compared the time required for the two formulations to equilibrate with the pH of simulated tear fluid and found that the pHast™ technology-based formulation underwent faster pH equilibration, achieving a final pH of 6.43 within 1 minute (starting pH: 4.35). 17 In contrast, the generic formulation, initially at pH 4.41, increased to pH 4.44 by the end of the 10-minute period.…”