Abstract
Glaucoma is a wide-spread eye disease caused by elevated intraocular pressure. Uncontrolled, this pressure may lead to damages to the optic nerve. Prostaglandin analogues, such as latanoprost and travoprost (which are water-insoluble active substances), are the most used class of active pharmaceutical ingredient. To administer them as eye drops, preservatives, such as benzalkonium chloride, are used as solubilizers. The latter is known to cause a local inflammation when used chronically and is not recommended for patients with ocular surface disorders. In this work, we sought to use polysorbate 80 (PS80) as a solubilizing agent simultaneously with sodium hyaluronate (NaHA) as a thickener and cytoprotective agent for the corneal surface. The first part of this study assessed the compatibility of the excipients with the active substance, using physicochemical methods such as spectra fluorescence and differential scanning calorimetry (DSC), as well as the solubilization mechanism of PS80 regarding prostaglandin analogues using nuclear magnetic resonance (NMR). The second part evaluated the stability of a formula candidate, its viscosity upon instillation, and its pharmacokinetic profile in rabbits as compared to the commercially approved medicine Travatan®. The results show that sodium hyaluronate is inert with respect to travoprost, while PS80 successfully solubilizes it, meaning that benzalkonium chloride is no longer required. Moreover, the pharmacokinetic profiles of the rabbits showed that the original formula described in the present study enhanced the ocular bioavailability of the drug, making it a promising product to control intraocular pressure with a potential reduced dosage of travoprost, therefore minimizing its related side effects.
Highlights
In the first part of this article, preformulation studies regarding the excipients of the formula NaHA and polysorbate 80 (PS80), and the active substance
PS80 and sodium hyaluronate were assessed as excipients in a preservativefree formulation of travoprost
PS80 was demonstrated to be a successful option to solubilize and stabilize travoprost in aqueous solution, while NaHA did not display any physicochemical interactions with travoprost and enhanced the rheological behavior of the formula
Summary
Primary open-angle glaucoma (POAG) is the second leading cause of blindness, affecting over 50 million people worldwide [1,2]. POAG is mainly induced by the accumulation of aqueous humour in the anterior chamber of the eye, causing elevated intraocular pressure (IOP). The increase in IOP causes mechanical stress to the posterior segment of the eye, and is correlated to retinal ganglion cell death [3]. POAG is insidious, as it is painless, i.e., the patients do not feel symptoms until damage is already done to the optic nerve fibers, resulting in irreversible vision loss [4,5]. Management of IOP is essential for the wellbeing of POAG patients
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