The Vitreous Model - a new in vitro test method simulating the vitreous body.

The vitreous body has become an interesting location for the administration of injections or implants in modern ophthalmology. Such intravitreal dosage forms are loaded with active agents which are released over a prolonged period of time. A test method simulating the in vivo situation is needed to observe the release behaviour of these new dosage forms and the distribution of drug substances in the vitreous humor. To simulate this situation the Vitreous Model (VM) was developed. The spherical glass corpus of the VM can be filled with a gel medium which is adapted to the in vivo situation. Gel insertion and sampling can be performed via a vent at the top. To simulate the movement of the eye the VM was placed on an altered orbital shaker. As vitreous substitute a modified polyacrylamide gel (PAA-gel), which consists of a 30% solution of acryl amide and standard Ringer buffer solution, was used. The water content, pH, relative density and refractive index of the PAA-gel were examined and compared to previous reported data for properties of human vitreous humor. For comparison the viscosity of the PAA-gel and porcine vitreous humor was determined experimentally. During a period of 3 hours the distribution behaviour of an injection of fluorescein sodium solution (1.25 mM) in the PAA-gel and in porcine vitreous humor was investigated by using the VM. The water content (99%) and pH (7.4) of the PAA-gel were equal to the values reported for porcine and human vitreous humor. Furthermore, the values obtained for the relative density (1.0013) and refractive index (1.3385) showed good accordances (deviation < 1%). Slight deviations were only found for the viscosity. Also in the distribution study a similar behaviour were detected. Along with the adapted shape of the VM, the new model seems suitable to perform in vitro experiments, which are capable of simulating in vivo conditions. Through the possibility of insertion of intravitreal injections and implants in the VM, biorelevant distribution and release studies may become feasible.