The Adaptation of a Millifluidics System for Ex Vivo Drug Absorption Studies

Before human trials are feasible, all drugs and their excipients must undergo vigorous scrutiny to assess potential health implications, safety, dosage and efficacy. Traditionally in all stages of drug research and development, the most predominant means of testing new drugs and formulations was by the in vivo study of animals. As time has progressed, the use of animals in research has become less accepted by society. A shift in public opinion ultimately led to a ban on testing cosmetic products and ingredients on animals. The clear sign of changing times has seemingly had an effect on many researchers in the pharmaceutical field who are turning their focus to developing and optimising animal-free models. An impressive 60% of the global market is accounted for by oral dosage forms; however, the complexity of the oral drug absorption route is difficult to replicate and has led to the development of many different types of gastrointestinal (GI) models. The choice of GI model is heavily debated among researchers with each model carrying its own benefits and limitations. Here, a modified millifluidics device containing viable ex vivo tissue combined with mass spectrometry imaging (MSI) and liquid chromatography tandem mass spectrometry (LC-MS/MS) has demonstrated its potential to be a useful workflow in drug absorption studies. The combination of MSI and LC-MS/MS has been used to explore the absorption of atorvastatin through porcine intestinal tissue along with the influence of relevant excipients. The adapted system has demonstrated the effect of excipients such as Mapcho-12 and DEGEE under different pH environments. The current adaptations made to the system pave the way for comparative studies to be performed within the same system using more valuable animal-free alternatives such as organoids and human biopsies. In turn, the model could help to bridge the gap for researchers exploring animal-free models. Further work has been identified to further improve the system which should be carried out before moving to more precious samples. The modular nature of the commercial system allows for further easy modifications to be made.