In vitro simulation of distribution processes following intramuscular injection

Abstract

There is an urgent need for in vitro dissolution test setups for intramuscularly applied dosage forms. Especially biorelevant methods are needed to predict the in vivo behavior of newly developed dosage forms in a realistic way. There is a lack of knowledge regarding critical in vivo parameters influencing the release and absorption behavior of an intramuscularly applied drug. In the presented work the focus was set on the simulation of blood perfusion and muscle tissue. A solid agarose gel, being incorporated in an open-pored foam, was used to mimic the gel phase of muscle tissue and implemented in a flow through cell. An aqueous solution of fluorescein sodium was injected. Compared to recently obtained in vivo results the distribution of the model substance was very slow. Furthermore an agarose gel of lower viscosity an open-pored foam and phosphate buffer saline pH 7.4 were implemented in a multi-channel-ceramic membrane serving as a holder for the muscle imitating material. Blood simulating release medium was perfused through the ceramic membrane including filling materials. Transport of the dissolved fluorescein sodium was, in case of the gel, not only determined by diffusion but also by convective transport processes. The more realistic the muscle simulating materials were constituted the less reproducible results were obtained with the designed test setups.

Keywords

• biorelevant
• flow-through-cell
• intramuscular injection
• in vitro dissolution