Maximization of the In Vitro transcorneal release and the In Vivo IOP-lowering effects of Latanoprost Ophthalmic gel formulations using Azone as a penetration enhancer and Carbopol-974 as a mucoadhesive

Abstract

The objectives of this study were to maximize; a) the in vitro transcorneal release, b) the IOP-lowering effect and, c) the duration of action, of Latanoprost acid (LAT) ophthalmic gels. Method. The in vitro transcorneal release of LAT from a 1st set of gel formulations that containing different concentrations of Azone™ (as enhancer) with fixed concentration of C-974® (as mucoadhesive) were studied. Then, formulation that showed greatest permeability parameters at lowest Azone™ concentration was selected for preparation of a 2nd set of ocular gels containing various C-974® concentrations. Similarly, their in vitro permeabilities were evaluated, and the best C-974® concentration required for preparation of formulation(s) that can be conceded as ideal ophthalmic LAT gel(s) was pinpointed.  Thereafter, the in vivo IOP-lowering efficacy study for the scaled-up formulations from both sets of the test formulations was conducted using TONO-PEN™ AVIA tonometer in rabbits for 4-consecutive days. Finally, how long such IOP-lowering effect does persist?  To answer this question, the most effective formulations were used for a single-dose study, and the IOP was assessed at predetermined time interval till re-establishing the IOP base-line. Results. Majority of tested formulations have showed significant but varied augmentations in both, in vitro and in vivo results. Formulations (GAZ-4) & GC-4 have shown the highest therapeutic IOP lowering effects; i.e., (7.8±1.8), (6.5±2.1), respectively. Particularly noteworthy with both formulations the IOP base-line didn’t re-established after 24 hours, and their durations of action in the single-dose study were 47±2.25, and 48±1.5, respectively. Conclusion. The in vitro release, onset, magnitude & duration of action of action of LAT gels have been enhanced and extended for up to 2-day with two gel formulations.  Nonetheless, the success in developing a novel ophthalmic formulation depended for great extent upon the crucial net outcomes of a very sensitive interplay/balance between the drug and additives.