Evaluation of two dynamic in vitro models simulating fasted and fed state conditions in the upper gastrointestinal tract (TIM-1 and tiny-TIM) for investigating the bioaccessibility of pharmaceutical compounds from oral dosage forms

Int J Pharm. 2016 Feb 10;498(1-2):178-86. doi: 10.1016/j.ijpharm.2015.11.048. Epub 2015 Dec 11.


Pharmaceutical research needs predictive in vitro tools for API bioavailability in humans. We evaluated two dynamic in vitro gastrointestinal models: TIM-1 and tiny-TIM. Four low-soluble APIs in various formulations were investigated in the TIM systems under fasted and fed conditions. API small-intestinal bioaccessibility profiles were evaluated between the two systems and in comparison with human data. Both TIM systems showed a higher bioaccessibility of ciprofloxacin and nifedipine during 3-4h after dosing immediate release (IR) compared to modified release (MR) formulations. Higher bioaccessibility levels from IR formulations were observed under fasted state in the first 30-90 min in tiny-TIM as compared to TIM-1, resulting in a tmax similar to clinical data. Absence (ciprofloxacin) or presence (posaconazole) of a food effect on bioaccessibility was observed in both TIM systems in line with human data. A higher bioaccessibility of fenofibrate from nano- vs micro-particle formulation was found in both TIM systems. This dataset shows the predictive quality of the TIM systems for clinical data on API small-intestinal bioaccessibility from IR and MR formulations and food effects. Tiny-TIM provides higher throughput and better prediction for IR formulations. TIM-1 provides detailed information on site-specific release of APIs, relevant for MR formulations and food effects.

Keywords: Food effect; In vitro gastrointestinal model; Oral dosage form; Pharmaceutical bioaccessibility; TIM system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Computer Simulation*
  • Diet, High-Fat / methods
  • Drug Evaluation, Preclinical / methods
  • Eating / drug effects
  • Eating / physiology
  • Fasting / metabolism*
  • Humans
  • Models, Biological*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism*
  • Postprandial Period / drug effects
  • Postprandial Period / physiology*
  • Upper Gastrointestinal Tract / drug effects
  • Upper Gastrointestinal Tract / metabolism*


  • Pharmaceutical Preparations