Gastrointestinal diseases and their impact on drug solubility: Crohn's disease

Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

“…A comparison of 5-ASA pharmacokinetics in healthy adults; adults with CD and adults with UC showed that the time to reach the colon was faster with greater overall exposure for the diseased patients compared to the healthy controls [55]. This increased exposure is likely to be due to a combination of factors: an increase in permeability due to the inflamed mucosa or the reduction in viscosity of the colonic fluids in patients with CD or UC or the greater frequency of propagating contractions in the colon [56,57].…”

Predicting budesonide performance in healthy subjects and patients with Crohn's disease using biorelevant in vitro dissolution testing and PBPK modeling

“…An overview of the experimental setup is given in Table 1. To reflect the differences in the composition of the gastrointestinal fluids of CD patients compared to healthy subjects, previously developed biorelevant media adapted to CD conditions were used for the in vitro release tests and prepared using the same method as for biorelevant media based on healthy subjects (Effinger et al, 2020). Since the development of CD biorelevant media followed a Design of Experiment (DoE) approach to reflect interindividual variability, several media have been developed for one prandial state and gastrointestinal compartment with different levels of the investigated factors in the DoE.…”

“…For poorly-soluble compounds, the use of biorelevant dissolution media, simulating closely the gastrointestinal fluid composition of healthy subjects, resulted in successful predictions of drug absorption (Berlin et al, 2014;Dressman and Reppas, 2000;Fotaki and Vertzoni, 2010;Sunesen et al, 2005). This approach has previously been extended to the pathophysiological conditions of patients with GI diseases and drug dissolution in CD can be simulated using these biorelevant media (Effinger et al, 2020).…”

Gastrointestinal diseases and their impact on drug solubility: Ulcerative Colitis

“…HPLC analysis was performed with an Agilent Technologies 1200 series HPLC system (Santa Clara, CA, US) with a binary pump, autosampler, thermostatted column compartment and diode array detector. The details of the HPLC-UV methods used for the quantitative analysis of the six compounds are described in Effinger et al (2020).…”