A level A in vitro/in vivo correlation in fasted and fed states using different methods: Applied to solid immediate release oral dosage form

Equipe de Recherche Technologique, Conception, Ingénierie et Développement de l'Aliment et du Médicament (ERT CIDAM), groupe biopharmaceutique, Faculté de pharmacie, 28 place Henri Dunant, 63000 Clermont-Ferrand, France.
European Journal of Pharmaceutical Sciences (Impact Factor: 3.35). 02/2006; 27(1):72-9. DOI: 10.1016/j.ejps.2005.08.006
Source: PubMed


The first purpose of this study was to simulate the impact of food intake on drug release and absorption in vivo using a novel in vitro system which mimics the gastro-intestinal (GI) tract in man. The drug studied was acetaminophen in the form of immediate release (IR) tablets. The second purpose was to establish a level A in vitro/in vivo correlation that could predict the bioavailability of a drug instead of using difficult, time-consuming and expensive in vivo bioequivalence studies. The artificial digestive system was used to estimate the availability of acetaminophen IR tablets for absorption in fasted and fed states. The same study was performed in vivo under similar conditions. A comparison study was carried out between the classical and the novel methods to estimate the efficacy of the new in vitro system to simulate the influence of food on drug release and absorption in vivo. A level A in vitro/in vivo correlation was established with a correlation coefficient of 0.9128 and 0.9984 in the fasted and fed states, respectively. Compared to USP II method, the novel in vitro model demonstrated a high level of efficacy in mimicking the behaviour of acetaminophen IR tablets in vivo in fasted and fed states.

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Available from: Stéphanie Blanquet-Diot, Oct 31, 2014
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    • "The TIM-1 system (TNO In-vitro gastro-intestinal Model) is a unique, validated, computer-controlled simulation of the stomach and small intestine with great reproducibility and application in studies of human health (Minekus et al., 1995, Minekus, 1998; Souliman et al., 2006). A detailed description of the TIM-1 system and methodology has been previously reported (Blanquet et al., 2004; Minekus et al., 2005; Faessler et al., 2006). "
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    ABSTRACT: Objectives Bioaccessibility is a useful measure for assessing the biological value of a particular nutrient from food, especially foods such as tubers. The wild tubers exploited by Hadza foragers in Tanzania are of interest because they are nontoxic, consumed raw or briefly roasted, and entail substantial physical barriers to consumers. In this study, we attempted to elucidate the biological value of Hadza tubers by measuring the absorption of glucose through in-vitro digestion. Methods We quantified digestibility using data from 24 experimental trials on four species of Hadza tuber using a dynamic in-vitro model that replicates digestion in the stomach and small intestine. Analysis of glucose in the input meal and output dialysate revealed the accessible glucose fraction. We also conducted assays for protein, vitamin, and mineral content on whole tubers and meal fractions. Results Bioaccessibility of glucose varies depending on tuber species. Holding effects of chewing constant, brief roasting had negligible effects, but high intraspecific variation precludes interpretive power. Overall, Hadza tubers are very resistant to digestion, with between one- and two-thirds of glucose absorbed on average. Glucose absorption negatively correlated with glucose concentration of the tubers. Conclusions Roasting may provide other benefits such as ease of peeling and chewing to extract edible parenchymatous tissue. A powerful factor in glucose acquisition is tuber quality, placing emphasis on the skill of the forager. Other nutrient assays yielded unexpectedly high values for protein, iron, and iodine, making tubers potentially valuable resources beyond caloric content.
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    ABSTRACT: The following chapter gives an overview of instrumented approaches to investigate the interactions of orally or pulmonary administered formulations with epithelial cell cultures in vitro. The first section is focused on the combined assessment of drug release/dissolution and subsequent absorp- tion/permeation for solid oral dosage forms. Experimental approaches to mimic the complex physiologically surroundings in the gastrointestinal tract are pre- sented as well as combinations of dissolution and permeation apparatus. The second part describes different experimental approaches to simultane- ously assess deposition and subsequent absorption of pharmaceutical aerosol formulations, typically by adapting some existing impactor/impinger devices to accommodate pulmonary epithelial cell culture systems. Differences between longtime and low-dose aerosol deposition in environmental toxicology and short time bolus inhalation of pharmaceutical aerosols are elucidated.
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