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.
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.
['Verwei|Miriam|M|', 'Minekus|Mans|M|', 'Zeijdner|Evelijn|E|', 'Schilderink|Ronald|R|', 'Havenaar|Robert|R|']
D000284:Administration, Oral D001682:Biological Availability D002626:Chemistry, Pharmaceutical D003198:Computer Simulation D059305:Diet, High-Fat D004353:Drug Evaluation, Preclinical D004435:Eating D005215:Fasting D006801:Humans D008954:Models, Biological D004364:Pharmaceutical Preparations D019518:Postprandial Period D041742:Upper Gastrointestinal Tract
Oral dosage form In vitro gastrointestinal model TIM system Food effect Pharmaceutical bioaccessibility