Abstract

DEVELOPMENT OF STABLE FORMULATION OF TRAVOPROST OPHTHALMIC SOLUTION 0.004%

Sapna Ramesh Pujari,* and Supriya S. Mahajan

Abstract

Travoprost, an insoluble prostaglandin is solubilized using a combination of surfactants, Polysorbate 80 and Solutol HS 15 (Macrogol 15 Hydroxystearate) to form a micellar solution. The marketed formulation, Travatan Z, uses Zinc as the preservative in a patented preservative system SofZia, which has potential to form precipitates due to interaction of Zn with one of the surfactants. In this work, potassium sorbate is used as a preservative and acceptable antimicrobial efficacy test was demonstrated at 80% and 100% of preservative concentration. The concentrations of sodium chloride and propylene glycol were optimized using a statistical experimental run using Design of Experiments in a Design Expert 9 software using a Central Composite Design using Response Surface method (RSM). Particle size of micelles (Z-average) and osmolality of the formulation were measured as responses. Effect of tubings, filters, sterilization of container closure system were evaluated and pH-Stability profile was generated. Bottles sterilized by ethylene oxide showed better stability than gamma sterilized bottles. The stability of the formulation is better as pH increases from 5 to 6. At an optimum pH of 5.7 the stability profile was compared with the marketed formulation Travatan Z and showed superior stability.

Keywords: Travoprost micelles, potassium sorbate, pH-stability, preservative efficacy, LDPE bottles.