Aqueous Prostaglandin Eye Drop Formulations

Abstract

Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the long-term treatment of open-angle glaucoma, prostaglandin analogues (PGAs) are the first-line treatment and are available as marketed eye drop formulations for intraocular pressure (IOP) reduction by increasing the trabecular and uveoscleral outflow. PGAs have low aqueous solubility and are very unstable (i.e., hydrolysis) in aqueous solutions, which may hamper their ocular bioavailability and decrease their chemical stability. Additionally, treatment with PGA in conventional eye drops is associated with adverse effects, such as conjunctival hyperemia and trichiasis. It has been a very challenging for formulation scientists to develop stable aqueous eye drop formulations that increase the PGAs’ solubility and enhance their therapeutic efficacy while simultaneously lowering their ocular side effects. Here the physiochemical properties and chemical stabilities of the commercially available PGAs are reviewed, and the compositions of their eye drop formulations are discussed. Furthermore, the novel PGA formulations for glaucoma treatment are reviewed.

Seeing the Future: A Review of Ocular Therapy

“…A common delivery modality for ocular therapeutics to treat anterior segment diseases, such as dry eye and glaucoma, is through eye drops [173,174,177]. The major disadvantage with eye drops is the leakage through the lacrimal system, an issue that can be resolved through the use of nanoparticle formulations.…”

“…Most of the current treatments for ocular surface diseases are eye drop formulations, including Miebo, Restasis, a cyclosporin drug, and Eysuvis, an ophthalmic suspension with loteprednol etabonate, all of which are FDA-approved treatments for dry eye disease [173][174][175][176]. Approved eye drops for use in glaucoma include prostaglandins such as latanoprost, travoprost, tafluprost, and bimatoprost, as well as Rho kinase inhibitors such as Netarsudil [177,178]. Additional glaucoma treatments are cholinergic agonists such as pilocarpine; alpha-adrenergic agonists including apraclonidine and brimonidine; beta blockers such as timolol; and carbonic anhydrase inhibitors such as dorzolamide [179][180][181].…”

A bibliometric analysis of apoptosis in glaucoma

“…However, at present, the only effective way to delay glaucoma progression is to reduce IOP using eye drops, surgery, or laser procedures (Schehlein and Robin, 2019 ; Rolim-De-Moura et al, 2022 ). Prostaglandins are the most common medication used to lower IOP by accelerating aqueous drainage through the uveal sclera (Jansook and Loftsson, 2022 ). Other drugs, such as α-adrenergic agonists, β-adrenergic blockers, and carbonic anhydrase inhibitors are second-line drugs that are ineffective in reducing IOP and have side effects (Lu et al, 2017 ; Nocentini and Supuran, 2019 ; Stoner et al, 2022 ).…”

Xalatan in the Treatment of Primary Open-Angle Glaucoma. Review

“…Простагландины (ПГ) представляют собой эйкозаноиды, полученные из арахидоновой кислоты и других полиненасыщенных жирных кислот, которые обладают разнообразной биологической активностью, включая расслабление гладкой мускулатуры. В целом, ПГ представляют собой липофильные, химически нестабильные и плохо растворимые в воде соединения в соответствии с химической структурой, состоящие из циклопентанового кольца с двумя боковыми цепями [7,8]. Первым зарегистрированным аналогом простагландина является латанопрост.…”