Search

We evaluated the usefulness of quality control dissolution data collected with compendial Apparatus I and II, biorelevant dissolution data collected with compendial apparatus IV, and bioaccessibility data collected with the non-compendial tiny-TIM system in screening modified release formulations during the development of BCS Class I compounds using a Boehringer Ingelheim model experimental compound, A6197. Four products were investigated: an immediate release tablet, an extended release tablet, modified release mini-tablets, and extended release pellets. Data with modified release products collected with the compendial apparatus were evaluated vs. the average intraluminal dissolution estimated after deconvoluting clinical data collected in healthy adults. Data collected with the tiny-TIM system were evaluated vs. the average AUC and Cmax values estimated from the clinical data. Unlike with the quality control data collected with Apparatus I and II, data collected with Apparatus IV data and Level I biorelevant media adequately described the intraluminal dissolution process of the three modified release products. Data deviated less than 10% from the actual average deconvoluted intraluminal dissolution profiles, illustrating the usefulness of Apparatus IV biorelevant data in understanding the intraluminal dissolution process of BCS class I small molecules administered as modified release products in the fasted state. Total bioaccessibility data and maximum bioaccessibility data collected using the tiny-TIM and the immediate release tablet and the three modified release drug products correctly reproduced the ranking of A6197 AUC values (R2 = 0.989) and Cmax values (R2 = 0.962), respectively, illustrating tiny-TIM as a useful system for formulation selection of BCS class I small molecules administered in the fasted state. © 2020 Elsevier B.V.

There is a need for information on the bioavailability in pediatric patients of drugs from manipulated dosage forms when applied in combination with food and/or co-medication under realistic daily practice circumstances. We describe the development, validation and application of a dynamic, computer-controlled in vitro system mimicking the conditions in the upper gastrointestinal tract of neonates, infants and toddlers: TIMpediatric. Paracetamol and diclofenac in age-related food matrices and with esomeprazole co-medication were tested. The experiments showed relevant results on the impact of drug manipulation and co-medication on the availability for absorption of active compounds. Without ethical constraints, alternative approaches for oral dosing and new pediatric formulations can be studied in TIMpediatric with a high predictive value. © 2013 Elsevier B.V.

Whole grain consumption has been linked to a lower risk of metabolic syndrome, which is normally associated with a lowgrade chronic inflammation. The benefits of whole grain are in part related to the inclusion of the bran, rich in phenolic acids and fiber. However, the phenols are poorly bioaccessible from the cereal matrix. The aim of the present study was to investigate the effect of bioprocessing of the bran in whole wheat bread on the bioavailability of phenolic acids, the postprandial plasma antioxidant capacity, and ex vivo antiinflammatory properties. After consumption of a low phenolic acid diet for 3 d and overnight fasting, 8 healthy men consumed 300 g of whole wheat bread containing native bran (control bread) or bioprocessed bran (bioprocessed bread) in a cross-over design. Urine and blood samples were collected for 24 h to analyze the phenolic acids and metabolites. Trolox equivalent antioxidant capacity was measured in plasma. Cytokines were measured in blood after ex vivo stimulation with LPS. The bioavailabilities of ferulic acid, vanillic acid, sinapic acid, and 3,4-dimethoxybenzoic acid from the bioprocessed bread were 2- to 3-fold those from the control bread. Phenylpropionic acid and 3-hydroxyphenylpropionic acid were the main colonic metabolites of the nonbioaccessible phenols. The ratios of pro-:antiinflammatory cytokines were significantly lower in LPS-stimulated blood after the consumption of the bioprocessed bread. In conclusion, bioprocessing can remarkably increase the bioavailability of phenolic acids and their circulating metabolites, compounds which have immunomodulatory effects ex vivo. © 2011 American Society for Nutrition. © 2011 American Society for Nutrition.

This study evaluated the potential of using ultra-fine grinding and electrostatic separation of wheat bran as methods to improve the bioaccessibility of para-coumaric acid (pCA), sinapic acid (SA) and ferulic acid (FA) from bran-rich breads. Bran fractions were produced and used to bake white bread, whole-grain bread, and seven different bran-rich breads. The influence of bran particle size and bread composition on the bioaccessibility of pCA, SA and FA was studied using a dynamic computer-controlled in vitro gastro-intestinal model. The amount of bioaccessible phenolic acids was higher in whole-grain bread and bran-rich breads than in white bread, and the finer the bran particles in bran-rich breads, the more bioaccessible the phenolic acids. The highest amounts of bioaccessible phenolic acids were observed for two of the fractions obtained by electrostatic separation of ground bran. Only the free and conjugated phenolic acids forms were found to be bioaccessible, and the bioaccessibility of SA was much higher than that of FA, due to the higher solubility of SA. This study demonstrated that the use of bran fractionation to reduce the particle size, or to include only some parts of the bran in foods, can help developing grain-based products with increased nutritional potential. © 2010 Elsevier Ltd.

Sinds eind jaren '70 zijn Europa en Amerika uit elkaar gegroeid in de waardering voor kerk en godsdienst. De Amerikaanse samenleving beleefde een religieuze wederopstanding, de Europese naties hielden vast aan de secularisatie. Dit verschil is voor een belangrijk deel te herleiden tot uiteenlopende reacties op de revolutie van de jaren '60.

Commercially available dry dog foods are often manufactured using extrusion cooking. Normal extrusion conditions can promote Maillard reactions involving the amino acid lysine. This non-enzymatic browning reaction occurs between a carbonyl group and an amino group in a diet. This study investigated the influence of a number of extrusion parameters for the manufacture of a dry dog food on the total and reactive lysine content. A 3×2×2 factorial design was used, with mass temperature (110°C, 130°C, and 150°C), diet moisture content (200 and 300 g/kg), and extrusion runs (once or twice) as variables. A diet formulated with wheat, maize, rice, chicken meat, poultry meal, and barley as the main ingredients (g/100 g dry matter |DM], including 23.3 crude protein, 11.3 crude fat, 53.1 starch, 0.6 ash, and 0.2 crude fiber) was extruded using a co-rotating twin-screw extruder (APV Baker MPF 50 [APV Baker, Peterborough, England]; length:diameter ratio: 25; screw speed: 15%; torque: 5% to 6%). Total lysine was measured by high-performance liquid chromatography (HPLC), and reactive lysine was determined by conversion of lysine by O-methylisourea (OMIU) to homoarginine, as described by Moughan and Rutherfurd.1 Total lysine content in the unprocessed diet was 0.98, and the OMIU-reactive lysine content was 0.70 of the total lysine content (0.69 g/100 g DM). The first extrusion run increased the ratio of OMIU-reactive lysine:total lysine, depending on extrusion temperature and moisture content. The ratio increased because of increased extrusion temperature. The higher moisture content lessened the increase in the ratio caused by increased temperature. Total lysine and other amino acids were unaffected by extrusion. The second extrusion run resulted in a lowering of the ratio of OMIU-reactive lysine:total lysine ratio when the ratio was close to 1.0. Ratios below 1.0 were further increased as a result of the second extrusion. Unprocessed canine diets can already have damaged lysine because of the use of heat-treated ingredients. Extrusion can have a variable effect on the OMIU-reactive lysine content of canine diets.

The nutritional quality of new functional or fortified food products depends on the bioavailability of the nutrient(s) in the human body. Bioavailability is often determined in human intervention studies by measurements of plasma or serum profiles over a certain time period. These studies are time and cost consuming and often appear to lack an optimal study design, leading to follow-up intervention trials. Therefore, an alternative approach is needed that will optimize the development of new products. This study describes an approach to predict human serum concentrations after the consumption of (fortified) food products. The concept is based on the integration of in vitro results with kinetic modeling. As a case study, human serum folate concentrations were predicted after the consumption of folate-fortified milk products for 4 wk. Oral bioavailability was investigated using a step-wise approach in which luminal bioaccessibility and intestinal absorption were independently evaluated. Subsequently, these in vitro data were integrated in a kinetic mathematical (in silico) model to predict serum folate concentrations after the intake of a single dose and during long-term consumption. This approach was evaluated in comparison to a human intervention study in which folic acid-fortified milk products were tested for their effect on serum folate concentrations. A high predictive quality of this alternative in vitro/in silico approach was demonstrated. Finally, this methodology was applied to predict serum folate concentrations after intake of different fortified milk products for 4 wk, showing its benefits for the development of new nutritional products. © 2006 American Society for Nutrition.

Mycotoxins such as aflatoxins, ochratoxins, trichothecens, zearalenone and fumonisins are presently considered economically and toxicologically important. Since these mycotoxins produce diseases in animals and humans, strategies have been undertaken to decontaminate mycotoxin-containing foodstuffs. One of the most recent approaches involves inert binders from different sources, such as hydrated sodium calcium aluminiosilicate (HSCAS), zeolites, smectites, sepiolite and activated carbons. When added to the feed they reduce mycotoxin toxicity in animals and carryover of mycotoxin from contaminated foodstuffs to animal products. Binders act by reducing the bioavailability of mycotoxins through adsorption on their surface. The efficacy of a binder is determined by critical parameters as affinity of the binder to the mycotoxin and the stability of the binder-mycotoxin complex, especially during gastrointestinal transit. The efficacy of mycotoxin adsorbents to reduce the bioavailability of mycotoxins in the gut, as well as their possible effect on the absorption of nutrients, is preferably studied in in vitro systems with a high predictive value for the in vivo performance. The reason is simple: it is not possible to perform studies in animals with all varieties of binders in different types of feed matrices. However, the question is: what is the relevance of the results from these in vitro systems in comparison to the situation in animals? This paper describes a dynamic, computer-controlled system which mimics the successive kinetic events in the gastrointestinal tract (GI tract) and has been validated in comparison to in vivo studies. Furthermore, we will demonstrate how TIM is applied in testing the efficacy of mycotoxin binders.