This dissolution method is also referred to as a “biorelevant transfer test”. It is designed to test how a drug product behaves when in contact with simulated gastric fluid (FaSSGF) which is subsequently converted into simulated intestinal fluid (FaSSIF). This experiment simulates the in vivo process when a drug product is transferred from the fasted stomach to the fasted intestine.

Similar to USP method

It is a similar principle to the USP two-tier dissolution test described in USP Chapter <711> (Method A Procedure). The main difference is that the acid and buffer stages used are biorelevant.

Equipment

This two-stage dissolution test is conducted in USP1/2 apparatus.

The media

Two media need to be prepared: FaSSGF (for the acid stage) and a FaSSIF Concentrate (for the buffer stage). Dissolution is first carried out in FaSSGF and then continued after converting the FaSSGF into FaSSIF using Two-stage FaSSIF. Before carrying out a two-stage biorelevant test, we strongly recommended first testing dissolution in FaSSIF (e.g. fasted intestinal fluid) to benchmark how the drug product is releasing prior to exposure to fasted stomach fluid. This is particularly important for drugs with low water solubility.

When to conduct the test

The test is mainly used during the development of drug products of water insoluble bases where solubility of the drug is higher in the gastric fluid than the intestinal fluid. The results reveal insights into precipitation or supersaturation as the pH is shifted from stomach to intestinal pH. The method is also used for enteric coated drug products where stability and release in the stomach fluid is tested prior to converting the fluid into intestinal fluid.