Physiologically-Based Pharmacokinetic (PBPK) Modelling Approach for the Prediction of Small Intestinal Precipitation of Poorly Soluble Drugs – A Simulation Study of Posaconazole Using the Simcyp ADAM Model

Author(s): Shriram M. Pathak, Bart Hens, Amitava Mitra, Nikunjkumar Patel, Bo Liu, Masoud Jamei, Joachim Brouwers, Patrick Augustijns, David B. Turner
Year:
  • Weakly basic poorly soluble drug compounds, such as posaconazole (POSA), may dissolve completely at fasted gastric pH but precipitate upon transit to higher small intestinal pH.
  • A number of in vitro and in vivo methods have been used to study intestinal precipitation of poorly soluble drug compounds with a varying degree of complexity.
  • This research work investigates the predictive capability of PBPK models to explore gastrointestinal (GI) luminal dissolution, supersaturation, and precipitation behaviour of POSA after oral administration of two suspension formulations (pH 7.1 and pH 1.6) in healthy volunteers.

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