Biorelevant dissolution models to assess precipitation of weak base drug

The impact of precipitation can affect the amount of drug absorbed, thereby affecting the amount of drug in the systemic body. The precipitation process is preceded by a supersaturation phase, caused by decreased drug solubility in the gastrointestinal tract. This precipitation occurs for weak base drugs with low solubility. When the drug entering the small intestine, the solubility of weak base drugs decrease, then occurs supersaturation, which leads to precipitation, so that drug precipitation is one of a challenge for the pharmaceutical industry in drug development. Precipitation testing of water-soluble weak base drugs can be carried out by the pH shift method to describe the gastrointestinal pH gradient from gastric to small intestine. This pH change can cause supersaturation and then trigger precipitation, especially for weak base drugs. The methods that can used to assess precipitation drug is modification of the USP dissolution which are two compartment and multi compartment model. The choice of dissolution medium play an important role in the test results. The use of bio relevant medium can produce closer in vitro and in vivo correlations than the use of buffers. Generally, the medium used to simulate the weakly condition in the small intestine is FaSSIF (Fasted State Simulated Intestinal Fluid) or FeSSIF (Fed State Stimulate Intestinal Fluid) medium. The medium used to simulate the acidic condition in the stomach is FaSSGF (Fasted state simulated gastric fluid) or FeSSGF (Fed state simulated gastric fluid) medium.