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Mechanistic prediction of food-induced variability in drug release and pharmacokinetics using a dynamic gastrointestinal system and convolution-based modeling - PubMed

4 hours ago
  • #Food Effect
  • #Sustained-Release
  • #Pharmacokinetics
  • The study uses a bioinspired dynamic human stomach-intestine system (DHSI-IV) to simulate gastrointestinal (GI) environments under different food conditions (fasted, milk, carbonated beverage, high-fat meal).
  • Gastric half-emptying times varied significantly, ranging from 16.7 minutes (water) to 90.2 minutes (high-fat meal), affecting drug dissolution rates for ibuprofen sustained-release capsules.
  • Dissolution results showed cumulative release of 42.1% (water), 33.15% (carbonated beverage), 41.95% (milk), and 44.35% (high-fat meal), highlighting prandial-dependent variability.
  • A convolution-based pharmacokinetic modeling approach predicted systemic exposure, aligning well with clinical data for fasted (Tmax and Cmax) and fed conditions (delayed absorption and increased AUC).
  • The DHSI-IV system is presented as a predictive tool for evaluating food effects on sustained-release formulations, aiding in formulation optimization and food-effect assessment.