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A. Kimura, H. Asada, N. Tuchimoto, K. kido, A. Shimazaki
Santen Pharmaceutical Co., Ltd
To evaluate the effects of pH and excipients on the chemical stability of Latanoprost and evaluate the feasibility of
stabilization of Latanoprost ophthalmic solution at room temperature.
The stability of Latanoprost (0.005%) in aqueous solutions at various pH conditions at 50ºC –80ºC was evaluated and the
shelf lives at room temperature were predicted by Arrhenius equation. The effect of some excipients on the stability of
Latanoprost was also evaluated. The accelerated stability study of Latanoprost ophthalmic solutions was performed at
40ºC/20%RH. Latanoprost and its degradant, the free acid form, were analyzed by HPLC method. Ocular hypotensive
efficacy of the stabilized Latanoprost ophthalmic solutions tested on ocular normotensive monkeys was compared with that
of Xalatan ophthalmic solution (0.005% Latanoprost commercial product) in a masked crossover study.
The chemical stability of Latanoprost was pH dependent and the main degradant was the free acid form generated by the
hydrolysis of isopropyl ester. Hydrolysis was more susceptible at less than pH 4 and at more than pH 6.7. The shelf life
(5% degradation at room temperature) was estimated more than 3 years at the range of pH 5.0-6.5. It was also clarified that
epsilon-aminocaproic acid was one of the best buffering agents. IOP lowering effects over 8 hours and the maximum IOP
reduction after the instillation of the stabilized formulation of Latanoprost ophthalmic solution and Xalatan ophthalmic
solution were equivalent.
It was clarified that the stabilization of Latanoprost in the ophthalmic solution at room temperature was feasible by the
selection of an optimum pH range and additives. Bio-equivalency of the stabilized formulation was also confirmed in the
monkey model.