Dissolution tests - Extended release (enteric coated)
Extended release formulations are intended to release the compound throughout the digestive tract in a constant way. Therefore it is useful to investigate the release and dissolution performance of such formulations under real digestive tract conditions. This can be done by apparatus, which are able to simulate the different compartments of the whole gut (stomach, small intestine, large intestine). The following section will demonstrate the some examples of using biorelevant solutions to investigate the behaviour of extended release formulations under physiological gut conditions.
BioDis (USP 3 apparatus)
The USP 3 apparatus (BioDis) can be utilised to investigate the quality and dissolution behaviour of delayed release formulations. It can simulate a transit of a compound through different sections of the digestive tract. This system can be used to test monolithic formulations such tablets, but also multiparticulate systems such as coated pellets.
The BioDis apparatus comprises 6 dissolution compartments with up to 8 rows per compartment. Up to 48 vessels can be placed in the BioDis. Each row is be filled with a biorelevant medium simulating a section of the digestive tract. For example, the first row would represent the stomach, the second row the duodenum, the third row the upper jejunum, etc. The extended release formulation is placed into a containment cell, which runs from row to row and is dipped into vessels simulating the different simulated gut sections. This simulated gut transit can help you to assess quality of your formulation and predict the dissolution behaviour of extended release dosage forms under physiological conditions.
In practice the BioDis vessels are filled with 200ml of biorelevant medium, placed in the apparatus and heated up to 37° C. The formulation is then placed in the containment cell. The dipping rate is programmed according to the section the formulation is in (e.g. 12 dips per minute in simulated stomach, 10 dips per minute in the simulated small intestine). Samples are drawn from the acceptor vessel with the help of a syringe (with sampling attachment and pre-filter) at defined time points. Then the samples are filtered through a low pore size filter (<0.45 µm) and prepared for analysis.
USP 4 apparatus / Flow-through tester
USP apparatus 4 (flow-through tester) is commonly used for the analysis of modified release dosage forms. An exchange of media is possible to simulate different environments of the digestive tract. It therefore represents another approach for the investigation of extended release formulations under biorelevant conditions.
A glass cell is used to hold the formulation. To simulate the transit of the formulation through different sections of the digestive tract (e.g. transit from the stomach into the intestine) an exchange of biorelevant media is required (e.g. FaSSGF exchanged by FaSSIF).
In practice the dissolution medium is warmed up to 37° C and pumped through the cell at a preset pumping rate, which depends on the simulated prandial state (e.g. with or without food) and gut segment (e.g. stomach, intestine). Samples are usually drawn via an internal sampling and filtration device.