Drug-like properties and topical delivery of rapalogs and tacrolimus in ophthalmology

Rapalogs, including sirolimus and everolimus, as well as tacrolimus, are macrolide immunosuppressants that have emerged as promising therapeutic agents in ophthalmology, offering novel approaches for managing various ocular diseases. However, their drug-like properties present significant challenges when administered topically to the eye. These compounds are practically insoluble in water and degrade relatively quickly once dissolved. Once in solution, they struggle to permeate mucus membranes due to their high molecular weight, ability to form multiple hydrogen bonds and high lipophilicity. Thus, formulating these drugs as eye drops that can deliver them topically to posterior eye segment and generate therapeutic drug concentrations in tissues like retina is challenging, if not impossible, without harming the permeation barriers. However, studies have shown that rapalogs and tacrolimus can be formulated as both aqueous and non-aqueous eye drops for treating conditions in the anterior eye segment. • Immunosuppressive macrolides in ophthalmology. • Drug-like properties and topical drug delivery to the eye. • The effects of physiochemical properties and thermodynamic activity on topical drug delivery. • Solubility and chemical stability of rapalogs and tacrolimus. • How to successfully deliver drugs from the eye surface into the eye.