Testing drug release from medicated contact lenses: The missing link to predict in vivo performance

Contact lenses (CLs) offer a wide variety of advantages as ocular drug-releasing platforms, but the feasibility of medicated CL development is constrained by numerous scientific, technological, and regulatory challenges. One main difficulty is the setting of release rate specifications for each drug, since at present there are no standardized in vitro release models that can appropriately predict the performance of drug-eluting CLs once placed onto the eye. CL-adapted release tests may provide knowledge on how the drug release pattern should perform in vivo to trigger and maintain the therapeutic effects for both anterior and posterior ocular tissues. Moreover, in vitro release tests are valuable tools for quality assessment during production and to investigate the effect of a change in composition or process variables. This review aims to shed light on biorelevant ways of evaluating in vitro drug release from CLs and the feasibility of establishing in vitro-in vivo correlations (IVIVC) to predict in vivo performance. First, general guidelines and Pharmacopeia release tests for topical ophthalmic formulations as well as in vitro release tests implemented for drug-CLs in the last two decades are analyzed. Then, development of an appropriate method to investigate IVIVC is attempted from the few papers simultaneously reporting in vitro release profiles and either in vivo release or therapeutic response. Finally, key points to be considered for in vitro testing drug release from a medicated CL are suggested to pave the way to the clinical arena. [Display omitted] •A variety of in vitro release conditions have been applied to test drug release from CLs•Most large-volume release tests fail to predict in vivo release and therapeutic outcome•Volume, dynamics and composition of release medium are key issues for designing biorelevant in vitro tests•Linear Levy plots of drug released in vivo vs. in vitro have been recorded using 2 mL of SLF•Microfluidic and 3D devices may better reproduce the ocular surface conditions, but in vivo validation is needed•Biorelevant in vitro tests may speed up the translation of efficient drug-releasing CLs to the clinics