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

Objectives The use of L-carnosine as an excipient in topical ophthalmic formulations containing gellan gum, a carbohydrate polymer with in-situ gelling properties upon mixing with mammalian tear fluid, was developed as a novel platform to extend precorneal duration. Specific utilisation of L-carnosine as a buffer in gellan gum carrying vehicles was characterised.

Methods Buffer capacity was evaluated using 7.5, 13.3, and 44.2 mM L-carnosine in a pH range of 5.5–7.5. Accelerated chemical stability was determined by HPLC at L-carnosine concentrations of 5–100 mM. Combinations of 7.5 mM L-carnosine with 0.06–0.6% (w/v) gellan gum were characterised rheologically. L-Carnosine-buffered solutions of gellan gum were tested for acute topical ocular tolerance in vivo in pigmented rabbits. A unique formulation combining timolol (which lowers intraocular pressure) in L-carnosine-buffered gellan gum was compared with Timoptic-XE in normotensive dogs.

Key findings L-Carnosine exhibited optimal pharmaceutical characteristics for use as a buffer in chronically administered topical ocular formulations. Enhancement trends were observed in solution-to-gel transition of L-carnosine-buffered vehicles containing gellan gum vs comparators. Topical tolerability of L-carnosine-buffered gellan gum formulations and lowering of intraocular pressure were equivalent with timolol and Timoptic-XE.

Conclusions Functional synergy between excipients in gellan gum formulations buffered with L-carnosine has potential for topical ocular dosage forms with sustained precorneal residence.