Caco-2 cell uptake of Ca, Mg and Fe from biscuits as affected by enrichment with pseudocereal/inulin mixtures

In vitro bioavailability/Caco-2 cell culture system was used to assess calcium, magnesium and iron bioavailability from different types of biscuits enriched with the mixtures of pseudocereals and legumes with inulin. Comparisons were made with the wheat flour based biscuit as a reference sample, in order to develope functional biscuit with improved mineral content, bioavailability and uptake. A significant increase of mineral content was achieved in all modified biscuits in relation to reference sample. Average bioavailability of investigated minerals ranged from 41.1% (Fe and Ca) up to 71.2% (Mg). Caco-2 cell uptake of investigated elements ranged from 7.13% to 12.20% for Fe; from 26.39% to 38.95% for Ca and from 19.65% to 27.17% for Mg. Inulin was determined as an important promoter of Ca and Mg bioavailability. Polyphenols and dietary fibre were determined as the principal components impairing the uptake of Fe and Ca. Enrichment of the reference recipe with the mixture of inulin with soy or amaranth flour positively influenced bioavailability/uptake of the investigated minerals

In vitro vs. canine data for assessing early exposure of doxazosin base and its mesylate salt

In this study, we evaluated the usefulness of biorelevant in vitro data and of canine data in forecasting early exposure after the administration of two phases of a BCS Class II compound, i.e., doxazosin base (DB) and its mesylate salt (DM). DB, DM, and doxazosin hydrochloride (DH) were prepared and characterized. In vitro data were collected in various media, including human aspirates. Solubilities of DB and DM in human gastric fluid were forecasted by data in fasted state simulating gastric fluid containing physiological components (FaSSGF-V2) but not by data in HCl pH 1.8. Unlike data in FaSSGF-V2, dissolution of DB and DM tablets in HCl pH 1.6 is rapid. Dissolution of DB tablet in FaSSGF-V2 is incomplete and conversion to DH seems to occur. Differences between DB and DM in dissolution in the small intestine are overestimated in the absence of physiological solubilizers. Using the in vitro data and previously described modeling procedures, the cumulative doxazosin profile in plasma was simulated and the 0-2 h profile was used for evaluating early exposure. Individual cumulative doxazosin profiles in plasma, after single DM tablet administrations to 24 adults, were constructed from corresponding actual plasma profiles. Compared with in vitro DM data in pure aqueous buffers, DM data in biorelevant media led to better prediction of early exposure. Based on intersubject variability in early exposure after DM administration and simulated profiles, the administered phase, DB or DM, does not have a significant impact on early exposure. Partial AUCs were used for evaluating early exposure after DB and DM administration in 4 dogs. Early exposure was significantly higher after administration of DM to dogs. Dogs are not appropriate for evaluating differences in early exposure after DB and DM administrations. © 2011 Elsevier B.V. All rights reserved

Intestinal permeability and excretion into bile control the arrival of amlodipine into the systemic circulation after oral administration

The objective of this study was to identify the factors controlling the arrival of amlodipine into the systemic circulation after oral administration in the fasting state. Dissolution data were collected with the rotating paddle and the flow-through apparatus. Caco-2 cell lines were used to assess the intestinal permeability characteristics. Actual in-vivo data were collected in 24 fasted healthy subjects after single-dose administration of the same amlodipine besylate tablet formulation used in the in-vitro dissolution studies. Regardless of the hydrodynamics, dissolution of amlodipine besylate tablets was rapid and complete in media simulating the contents of the upper gastrointestinal tract in the fasting state. Permeability of amlodipine through Caco-2 cell lines was lower than propranolol's and higher than ranitidine's, indicating that transport through the intestinal mucosa may be one process that limits the arrival into the systemic circulation. Indeed, the deconvoluted profile indicated that arrival into portal blood occurs at rates much slower than gastric emptying or dissolution rates. However, prediction of amlodipine's mean plasma profile after oral administration became possible only after additionally assuming excretion of amlodipine into the bile and a reasonable gastrointestinal residence time. Interestingly, in-vitro permeability data collected in this or in previous studies were inappropriate for simulating the mean actual plasma profile. © 2006 The Authors