Novel Dissolution Testing By BMS
In this post you can learn more about novel biorelevant dissolution testing methods performed by Bristol-Myers Squibb and used to assess pH-dependency of NCEs.
Testing pH-dependency for new chemical entities (NCEs) that are weak bases is vital as it can have a big impact on how well they perform in the gut. Due to reduced dissolution rate and/or solubility, weak bases are likely to present reduced absorption in the gut or large pharmacokinetic variability (affecting a drug’s performance and its toxicity) especially in patients with lower gastric secretion. Having a clear idea of pH-dependency of the API is important for formulation development and for toxicology formulations to minimize these issues. At Bristol-Myers Squibb, Mathias et al. developed a system to predict in vivo pH-dependency from in vitro dissolution testing in Biorelevant Media¹. They used physiologically based pharmacokinetic modelling (PBPK) to link the dissolution values from 14 weakly basic compounds to pre-existing clinical data.
What’s very interesting is that they found that this system using Biorelevant Media is a better predictor than simply looking at the correlation between physicochemical properties and clinical pH-effect, which have no linear correlation. This novel in vitro dissolution test means that, based on a combination of dissolution and in silico modelling, a weakly basic compound can be classified as high, moderate or low risk in terms of drug precipitation and selection. This would be really useful for anyone involved in salt selection and formulation development. Want to know more? Check out the original article referenced below!
1. Mathias, N. R. et al. Assessing the risk of pH-dependent absorption for new molecular entities: A novel in vitro dissolution test, physicochemical analysis, and risk assessment strategy. Mol. Pharm. 10, 4063–4073 (2013).