The VitraCell: A new in vitro test setup for intravitreal dosage forms.

The population is aging, which is accompanied by an increasing prevalence of ocular diseases that require novel intravitreal therapeutic options. Preclinical studies for new intravitreal therapies are typically conducted in animals. Appropriate biorelevant in vitro models could replace, reduce and refine (3R) these in preclinical testing. Therefore, the VitraCell was developed as a new in vitro vitreous body model and adapted to certain physiological conditions. It consists of a central vitreous compartment filled with an optimized vitreous substitute composed of 0.22 % hyaluronic acid and 0.09 % agar. Two lateral chambers are connected to this central compartment, each representing a closed buffer circulation system with an associated buffer reservoir. The release, diffusion, and elimination characteristics of various active pharmaceutical ingredients and dosage forms, including implants containing triamcinolone acetonide and paracetamol, as well as a triamcinolone acetonide suspension, were investigated following simulated intravitreal injection. Distinct differences were identified, indicating the general suitability of the system. In addition, initial comparisons with in vivo literature data appear promising. Furthermore, sufficient stability of the vitreous substitute over a diffusion period of three weeks was demonstrated. In addition, comparative measurements were performed using compendial pharmacopeial methods, namely United States Pharmacopeia Apparatus 4 and 7. These methods exhibited markedly faster and probably physiologically less relevant release rates, further highlighting the suitability of the VitraCell, which therefore represents an additional step toward an optimized biorelevant in vitro test setup for intravitreal dosage forms.