A stable fixed-dose combination of benzalkonium chloride-free latanoprost and once-a-day timolol

Abstract

Objective This study outlines the development of a stable fixed dose combination solution formulation of Benzalkonium chloride (BKC)-free latanoprost with once-a-day timolol in a gel-free reservoir (GFR) vehicle. Methods A fixed-dose combination (FDC) formulation of latanoprost and timolol maleate was prepared by mixing polymers, buffers, and ionic preservatives followed by parylene coating of plastic bottles that were used for stability studies. Key findings The FDC formulation was a clear, colorless, slightly viscous solution. The adsorption of latanoprost on the parylene coated plastic bottle surface was reduced. Promoting stability for 36 months. The assay and impurities and other physicochemical quality attributes, such as color, clarity, osmolality, and pH met the required standards of both latanoprost and timolol. The sterility and antimicrobial effectiveness testing (AET) also complied with the United States Pharmacopeia (USP) requirements. Stability was proven for 30 days in simulated in-use conditions. It showed clinically relevant (>2 mm Hg) intraocular pressure (IOP) reduction in a normotensive dog model. It also showed an higher IOP reduction (efficacy) over individual or concomitantly administered drug components and numerically better IOP reduction than the marketed FDC formulation in a conventional vehicle. Faster action was seen within 2-h on first day and recovery took 5 days post treatment cessation. Conclusion A stable FDC formulation in parylene-coated plastic bottles was successfully developed meeting the clinically relevant IOP reduction criteria. Comparable efficacy insptto existing treatment, this FDC is preferable option for patients with conditions such as dry eye and ocular surface disease.