Novel in vitro model for intravitreal drug dissolution and release studies of small molecules and their long-acting formulations

Abstract

Intravitreal drug delivery is essential for multiple ocular diseases. Development of intravitreal formulations requires high-quality in vivo experiments that require a large number of animals. This development can be expedited by improving in vitro testing and utilizing in vitro – in vivo correlation. We propose an in vitro approach using vitreous in a dialysis membrane to conduct these studies. The model was developed for small molecules and evaluated with drugs in solution (13 drugs in one cassette and 4 in another), and a drug suspension. For solutions, 6 out of 8 drug compounds were within 2.5-fold difference to their experimental vitreal clearances. Furthermore, we demonstrated suitability of the model for long-acting formulations in a 150-day experiment with triamcinolone acetonide suspension. The suspension displayed similar elimination trend as has been observed in rabbits. We believe this system can lead the way in introducing site-specific drug release testing for the intravitreal route.