During the development of oral drug formulations, it’s important to find out if the right drug concentration arrives at the desired place of action.

Drug absorption is measured in vivo, in other words in a human (or animal) body. Typical in vivo indicators are ‘time – blood plasma concentration profiles’ of drugs after oral administration. To identify the parameters involved in drug absorption in vitro investigations are usually performed. In vitro literally means ‘in glass’ and depicts an investigation performed in an artificial environment mimicking a biological condition.

To establish a reliable in vitro in vivo relationship (IVIVC) it is important that the artificial environments simulate the biological conditions as closely as possible. On that basis the experimental results can directly be connected to real outcomes in humans. During drug development and formulation exploration, in vitro solubility and dissolution should artificially mimic the in vivo drug or formulation performance in the human gastrointestinal tract. The in vitro results are then related to in vivo drug plasma concentration profiles (see danazol example below). When an in vitro in vivo correlation is established, it is used for development and optimisation of drug formulations. Research organisations often use this method to reduce costly and time intensive trials on animals and humans during formulation development.

Nowadays computer models are often used to link in vitro results with in vivo outcomes. These so called physiologically based pharmacokinetic (PBPK) models are capable of translating in vitro results into in vivo predictions. This method is defined as in vitro in silico in vivo correlation (IVISIVC).

Establishing in vitro in vivo correlations for poorly soluble drugs (also referred as BCS Class II and IV) can be challenging. When it comes to investigation of drug dissolution performance in the simulated conditions of the gastrointestinal tract, simple buffers usually are not sufficient enough. In this case, Biorelevant Media should be utilized because they closely mimic the fluids of the human (and animal) stomach and intestine. Biorelevant Media have become the gold standard for IVIVC and IVISIVC investigations of poorly soluble drugs during formulation development.