L-Carnosine: multifunctional dipeptide buffer for sustained-duration topical ophthalmic formulations

Area of Science:

• Ophthalmology
• Pharmaceutics
• Materials Science

Background:

• Topical ophthalmic formulations aim to prolong precorneal residence time for sustained drug delivery.
• Gellan gum is a carbohydrate polymer that forms in-situ gels upon contact with tear fluid.
• L-carnosine is explored as a novel excipient for its buffering capacity and potential synergistic effects.

Purpose of the Study:

• To develop and characterize l-carnosine as a buffer in gellan gum ophthalmic formulations.
• To evaluate the impact of l-carnosine on the in-situ gelling properties and stability of gellan gum.
• To assess the ocular tolerability and efficacy of l-carnosine-buffered gellan gum formulations.

Main Methods:

• Buffer capacity of l-carnosine was assessed across a pH range.
• Chemical stability of l-carnosine was determined using HPLC.
• Rheological characterization of gellan gum formulations with l-carnosine.
• In vivo ocular tolerance testing in rabbits and efficacy study in dogs comparing timolol formulations.

Main Results:

• L-carnosine demonstrated optimal buffering characteristics for ophthalmic use.
• Formulations showed enhanced solution-to-gel transition with l-carnosine.
• L-carnosine-buffered gellan gum formulations were well-tolerated and effectively reduced intraocular pressure.

Conclusions:

• A functional synergy exists between l-carnosine and gellan gum in ophthalmic formulations.
• This buffered system offers potential for sustained precorneal residence and improved topical ocular drug delivery.