SCREENING AND SELECTION OF SURFACTANTS FOR SOLUBILIZATION OF TRAVOPROST USING DESIGN OF EXPERIMENTS

*Sapna Ramesh Pujari, Kavita Inamdar and Supriya S. Mahajan

ABSTRACT

Travoprost is a prostaglandin analogue widely used for reducing intraocular pressure (IOP) in patients affected with glaucoma and ocular hypertension. The current marketed formulation of Travoprost 0.004% in the US (Travatan Z) is a micellar solution with an ionically buffered preservative system Sofzia, recommended for treatment of open angle glaucoma. This formulation has several disadvantages and has the potential to form particulate matter during its shelf life due to interaction with the preservative system. The current marketed formulation also uses a patented primary packaging component to stabilize the formulation. Thus, an effort was made to select alternate surfactants for dissolving Travoprost in micellar solutions. Design of Experiments was used for screening a combination of four surfactants namely, Cremophor RH 40, Cremophor EL, Polysorbate 80 and Solutol HS 15 using Optimal Custom Mixture design. Particle size and polydispersity index (PDI) were measured as responses. A combination of two surfactants was chosen based on the lowest polydispersity index. Further optimization of surfactant concentrations was done using a Response Surface Optimal design. The results of particle size and PDI were evaluated statistically using regression analysis. All the experiments gave a particle size in the nano range of less than 20nm.

Keywords: Travoprost, Micellar solution, Surfactants, Design of experiments, particle size, Polydispersity Index.