Prediction of the in vivo performance of enteric coated pellets in the fasted state under selected biorelevant dissolution conditions

摘要

The purpose of this research was to predict the in vivo dissolution of lansoprazole from enteric coated pellets in the fasted state using a biorelevant flow-through dissolution method with low flow rates and volumes close to those in vivo. Additionally, a novel rotating stirring element, composed from magnet inserted in a silicone tube, was used to produce the movement of the pellets and expose them to slightly increased physical stress. Obtained dissolution results were compared to the dissolution results of our previous work using the USP IV with higher flow rate (11 ml/min). As drug release from enteric coated pellets usually starts in the small intestine, the influence of pellets' residence time in the gastric medium and additionally the effect of different media on drug release was studied. Prolongation of residence time in an acidic medium had only minor effect on the release rate after initial lag time, but significantly reduced the total amount of the drug released from both tested formulations, which was attributed to the drug's degradation in an acidic medium. The increased physical load on the pellets induced by the rotating stirring element compensated for the decrease of flow rate from 11 ml/min using the USP IV to 3 ml/min using the non-compendial system. Considering also gastric emptying kinetics good prediction of the in vivo release was achieved compared to in vivo absorption data obtained from a pharmaco-kinetic study under fasting conditions. Thus, using more physiologically relevant dissolution conditions, expressed through low volume and lower flow rate, and in combination with increased mechanical stress we obtained equally good in vitro/in vivo correlation as using USP IV and higher flow rates. Comparison of the dissolution results obtained with two different systems provided additional insight into product behaviour and improved prediction of in vivo performance.