Journal of Chemical Engineering of Japan, Vol.35, No.5, 450-455, 2002
In vivo/in vitro correlation of intravitreal drug delivery from biodegradable polymer implants
An approach for predicting the drug concentration in the vitreous body has been proposed for intravitreal drug delivery by biodegradable polymer implants. The release rates of a model drug, dexamethasone sodium m-sulfobenzoate (DMSB), from poly lactic acid implants were measured under in vitro and in vivo conditions using Japanese albino rabbits. The pharmacokinetic model assuming the cylindrical vitreous body was then solved together with the in vivo release rate and the other model parameters determined separately. The mathematical model successfully described the drug concentration-time profile in the vitreous body. The in vivo concentration-time profile in the rabbit vitreous body agreed with the one predicted on the basis of the in vivo release profile. The in vivo concentration-time profile in the vitrectomized eye was well predicted from the in vitro release profile. These findings may suggest that if the in vivo release profile is known or predicted, the in vivo concentration in the vitreous body can be evaluated by the help of computer simulation without carrying out them vivo release experiment which is usually time-consuming for controlled release formulations.
Keywords:intravitreal delivery;in vivo/in vitro correlation;pharmacokinetic model;dexamethasone sodium;m-sulfobenzoate;poly(DL-lactic acid);biodegradable polymer