Application of tiny-TIM as a mechanistic tool to investigate the in vitro performance of different itraconazole formulations under physiologically relevant conditions

Mármol, Álvaro López; Fischer, Paulina L; Wahl, Andrea; Schwöbel, Daniela; Lenz, Verena; Sauer, Kerstin; Koziolek, Mirko

doi:10.1016/j.ejps.2022.106165

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…A dialysis membrane is integrated at the end of the small intestinal compartment, which consists of two sections, in order to study the bioavailability of water-soluble compounds. The schematic design was described previously . Parameters such as the luminal temperature (37 °C), chyme transit, peristaltic movements, stomach and intestinal pH, addition of secretion fluids (gastric and pancreatic enzymes, bile, hydrochloric acid, bicarbonate), and dialysis of digestion products are computer-controlled and mimic conditions of human digestion …”

Section: Methodsmentioning

confidence: 99%

“…The schematic design was described previously. 35 Parameters such as the luminal temperature (37 °C), chyme transit, peristaltic movements, stomach and intestinal pH, addition of secretion fluids (gastric and pancreatic enzymes, bile, hydrochloric acid, bicarbonate), and dialysis of digestion products are computer-controlled and mimic conditions of human digestion. 22 A tiny-TIMsg protocol for protein digestion was followed, which was based on a meal intake of 150 g. All plant-based drinks and the cow's milk had pH values ranging from 6.4 to 7.1, and no pH adjustment was made.…”

Section: Test Productsmentioning

confidence: 99%

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Bioaccessibility and Digestibility of Proteins in Plant-Based Drinks and Cow’s Milk: Antioxidant Potential of the Bioaccessible Fraction

Khamzaeva,

Kunz,

Schamann

et al. 2024

J. Agric. Food Chem.

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During the last years, a strong increase in the sales volume and consumption of plant-based drinks was observed, which were partly used as an alternative to cow’s milk. As milk is a relevant protein source in many countries, we have investigated the protein bioaccessibility and digestibility of soy, almond, and oat drinks in comparison to milk using the tiny-TIMsg gastrointestinal model. The relative protein digestibility of all products was between 81% (soy drink) and 90% (milk). The digestible indispensable amino acid score (DIAAS) in vitro method was used to estimate the protein nutritional quality. The highest DIAAS values were obtained for milk in tryptophan (117%) and soy drink in sulfur containing amino acids (100%). Oat drink was limited in lysine (73%), almond drink in lysine (34%) and the sulfur containing amino acids (56%). Additionally, the antioxidant activity of the bioaccessible fractions was analyzed using Trolox equivalent antioxidative capacity and oxygen radical absorbance capacity assays, revealing a higher antioxidative potential of milk and soy drink compared to oat and almond drink.

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Section: Methodsmentioning

confidence: 99%

Section: Test Productsmentioning

confidence: 99%

Bioaccessibility and Digestibility of Proteins in Plant-Based Drinks and Cow’s Milk: Antioxidant Potential of the Bioaccessible Fraction

Khamzaeva,

Kunz,

Schamann

et al. 2024

J. Agric. Food Chem.

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“…While TIM-1 is considered one of the most advanced systems for biopredictive dissolution, to use the data acquired from TIM-1 experiments to their full potential, additional analysis may be needed. Several studies have explored in vitro–in vivo (IVIVC) correlations using TIM-1 or Tiny-TIM and PBBM models. − However, in complex situations, in vitro–in vivo correlation may be challenging to establish. For example, bioaccessibility results alone may not confirm whether precipitation of a weak base has taken place in the duodenal compartment in the fasted state.…”

Section: Introductionmentioning

confidence: 99%

“…In cases where detailed information on the events in TIM-1 lumen is required, sampling directly from the compartments can be done. For example, in a recent study, 23 a luminal sampling approach was employed to assess the performance of different itraconazole formulations. Luminal concentrations can provide in-depth insight into drug product performance.…”

Section: ■ Introductionmentioning

confidence: 99%

Digitalizing the TIM-1 Model using Computational Approaches–Part One: TIM-1 Data Explorer

Sarcevica,

Hens,

Tomaszewska

et al. 2023

Mol. Pharmaceutics

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The TIM-1 gastrointestinal model is one of the most advanced in vitro systems currently available for biorelevant dissolution testing. This technology, the initial version of which was developed nearly 30 years ago and has been subject to a number of significant updates over this period, simulates the dynamic environment of the human gastrointestinal tract, including pH, transfer times, secretion of bile, enzymes, and electrolytes. In the pharmaceutical industry, the TIM-1 system is used to support drug product design and provide a biopredictive assessment of drug product performance. Typically, the bioaccessibility data sets generated by TIM-1 experiments are used to qualitatively compare formulation performance, and the use of bioaccessibility data as inputs for physiologically based pharmacokinetic (PBPK) modeling for quantitative predictions is limited. To expand the utility of the TIM-1 model beyond standard bioaccessibility measurements (which define the fraction available for absorption), we have developed a computational tool, TIM-1 Data Explorer, to describe the fluid and mass balance within the TIM-1 system. The use of this tool allows a detailed inspection and in-depth interpretation of the experimental data. In addition to mass balance calculation, this model also can be used to describe the critical processes a drug substance would undergo during a TIM-1 experiment, such as dissolution, precipitation on transfer from the stomach to duodenum, and redissolution. The TIM-1 Data Explorer was validated in two case studies. In the first case study with paracetamol, we have shown the ability of the simulator to adequately describe mass transfer events within the TIM-1 system, and in the second study with a weakly basic in-house compound, PF-07059013, the TIM-1 Data Explorer was successfully used to describe dissolution and precipitation processes.

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Application of biorelevant in vitro assays for the assessment and optimization of ASD-based formulations for pediatric patients

Niessen¹,

Mármol²,

Ismail³

et al. 2023

European Journal of Pharmaceutics and Biopharmaceutics

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Application of tiny-TIM as a mechanistic tool to investigate the in vitro performance of different itraconazole formulations under physiologically relevant conditions

Cited by 7 publications

References 29 publications

Bioaccessibility and Digestibility of Proteins in Plant-Based Drinks and Cow’s Milk: Antioxidant Potential of the Bioaccessible Fraction

Bioaccessibility and Digestibility of Proteins in Plant-Based Drinks and Cow’s Milk: Antioxidant Potential of the Bioaccessible Fraction

Digitalizing the TIM-1 Model using Computational Approaches–Part One: TIM-1 Data Explorer

Application of biorelevant in vitro assays for the assessment and optimization of ASD-based formulations for pediatric patients

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