New Preservative-Free Formulation for the Enhanced Ocular Bioavailability of Prostaglandin Analogues in Glaucoma

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.

Enteric-coating film effect on the delayed drug release of pantoprazole gastro-resistant generic tablets

“…The FTIR spectra for both the generic and brand products showed similarities in the band positions when compared to the reference pure powder, suggesting that there was no interference between the drug molecule and the excipients used in both products and confirming the presence of the PNZ drug molecule in both. 60 , 75 , 76 However, differences in band transmittance were observed between the generic and brand samples, which could be attributed to the presumed presence of impurities in the generic PNZ product. 55 , 76 – 77 These findings are consistent with previous literature that reported no alteration in the band position for PNZ in the formulation, except for the band transmittance.…”

Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases

“…Prostaglandin analogues, which are medications that are poorly soluble in water, are typically coupled with preservatives, such as benzalkonium chloride or polyquaternium, to make them more soluble. However, repeated instillation of these medications may irritate the ocular surface [ 74 ]. Thus, employment of nanocarriers into the formulation of prostaglandin analogues would reduce the dependence on the solubilization effect of the preservative and could lead to the development of preservative-free formulations [ 75 ].…”

Polymer-Based Self-Assembled Drug Delivery Systems for Glaucoma Treatment: Design Strategies and Recent Advances

“…At present, one of the methods to achieve higher viscosity is by using polymer thickeners, such as hyaluronic acid, polyvinyl alcohol, cyclodextrin, and others [41]. For example, Alviset et al employed sodium hyaluronate as a thickener and polysorbate 80 as a surfactant to selfassemble the system into micelles to load the drug, enhancing the performance of the eye drops, leading to a reduced dose of travoprost in the eye drops while improving bioavailability in rabbits and minimizing side effects [42]. Furthermore, nano or micro-structures formed by polymer self-assembly can not only increase the viscosity of the solution but also be applied as a carrier to controllably deliver the drugs.…”