Search results for "absorption."
showing 10 items of 2682 documents
Fasted-state simulated intestinal fluid "FaSSIF-C", a cholesterol containing intestinal model medium for in vitro drug delivery development.
2015
A set of biorelevant media "fasted-state simulated intestinal fluid with cholesterol (FaSSIF-C)" for the in vitro study of intestinal drug dissolution in the duodenum was developed. These contain cholesterol at the same levels as in human bile: the cholesterol content of FaSSIF-7C is equivalent to healthy female, FaSSIF-10C to healthy male persons, and FaSSIF-13C to several disease cases that lead to gallstones. The fluids were studied in three aspects: biocompatibility, intestinal nanostructure, and solubilizing power of hydrophobic drugs of the BCS class II. The biocompatibility study showed no toxic effects in a Caco-2 cell system. The drug-solubilizing capacity toward Fenofibrate, Danaz…
Intestinal cholesterol absorption: identification of different binding proteins for cholesterol and cholesterol absorption inhibitors in the enterocy…
2003
Absorption of cholesterol from the intestine is a central part of body cholesterol homeostasis. The molecular mechanisms of intestinal cholesterol absorption and the proteins mediating membrane transport are not known. We therefore aimed to identify the proteins involved in intestinal cholesterol absorption across the luminal brush border membrane of small intestinal enterocytes. By photoaffinity labeling using photoreactive derivatives of cholesterol and 2-azetidinone cholesterol absorption inhibitors, an 80-kDa and a 145-kDa integral membrane protein were identified as specific binding proteins for cholesterol and cholesterol absorption inhibitors, respectively, in the brush border membra…
Kinetics of zinc transport in vitro in rat small intestine and colon: interaction with copper.
2002
The present study was planned to investigate the kinetic transport of zinc, in the intact intestine of the rat, in order to establish if more than one transporter is involved as well as the existence of a preferent sector in the cation uptake. Using an in vitro technique, the influx of zinc across the brush border membrane in three sectors of the small intestine (proximal, mid and distal) and in the colon of the rat was measured at six different concentrations (from 0.0007 to 11 mM). The kinetic study showed that intestinal transport of zinc occurs by a saturable process in the small intestine. The K(m) value obtained in the proximal segment (10.78+/-4.40 mM) is clearly higher than those ob…
Dissolution and dissolution/permeation experiments for predicting systemic exposure following oral administration of the BCS class II drug clarithrom…
2017
In order to save time and resources in early drug development, in vitro methods that correctly predict the formulation effect on oral drug absorption are necessary. The aim of this study was to 1) evaluate various BCS class II drug formulations with in vitro methods and in vivo in order to 2) determine which in vitro method best correlates with the in vivo results. Clarithromycin served as model compound in formulations with different particle sizes and content of excipients. The performed in vitro experiments were dissolution and dissolution/permeation experiments across two types of membrane, Caco-2 cells and excised rat intestinal sheets. The in vivo study was performed in rats. The oral…
Mechanistic basis for unexpected bioavailability enhancement of polyelectrolyte complexes incorporating BCS class III drugs and carrageenans
2013
The objective of this study was to investigate the potential of λ-carrageenan to work as an absorption modifying excipient in combination with formulations of BCS class 3 substances. Trospium chloride was used as a model BCS class 3 substance. Polyelectrolyte complexes of trospium and λ-carrageenan were produced by layer-by-layer complexation. A λ-carrageenan-containing formulation was administered either in capsules size 9 to rats by gavage or directly into ligated intestinal loops of rats. Exceptionally strong variations were observed in the plasma concentrations of the rats that received λ-carrageenan compared to the control group, but enhanced plasma concentrations were observed only in…
Unique pharmacology of KAR-2, a potential anti-cancer agent: absorption modelling and selective mitotic spindle targeting.
2008
Abstract Bis-indols are a large group of the anti-cancer agents, which effectively arrest the uncontrolled division of the cancerous cells. Their use in clinical chemotherapy is still limited because of: (i) the non-specific targeting of the mitotic cells; (ii) low bioavailability of the drugs. KAR-2 has been identified as a tubulin binding agent which displays significantly lower cytotoxicity but favourable anti-cancer potency than its mother molecule, vinblastine. The objective of this paper, on one hand, was to show that the human intestinal epithelial Caco-2 cells, used for pharmacokinetic studies display distinct sensitivity against KAR-2 and vinblastine due to their distinct targeting…
IVIVC in oral absorption for fenofibrate immediate release tablets using a dissolution/permeation system.
2009
ABSTRACT: The usefulness of a dissolution/permeation (D/P) system to predict the in vivo performance of solid dosage forms containing the poorly soluble drug, fenofibrate, was studied. Biorelevant dissolution media simulating the fasted and fed state conditions of the human gastrointestinal tract were used in order to simulate the effect of food on the absorption of fenofibrate. Moreover, the results obtained from the D/P system were correlated with pharmacokinetic parameters obtained following in vivo studies in rats. The in vitro parameter (amount permeated in the D/P system) reflected well the in vivo performance in rats in terms of AUC and C max of fenofibric acid. This study thus demon…
Assessment and modulation of acamprosate intestinal absorption: comparative studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo mode…
2003
The purpose of this study was to explore the intestinal absorption mechanism of acamprosate and to attempt to improve the bioavailability (BA) of the drug through modulation of its intestinal absorption using two enhancers (polysorbate 80 and sodium caprate) based on in situ, in vitro and in vivo models and comparing the results obtained. Intestinal transport of the drug, in the absence and in presence of polysorbate 80 (0.06, 0.28 and 9.6 mM) or sodium caprate (13 and 16 mM) was measured by using an in situ rat gut technique and Caco-2 cell monolayers. Additionally, the effect of sodium caprate on drug oral bioavailability, measured as urinary recovery, was quantified by performing in vivo…
Freeze-dried eudragit-hyaluronan multicompartment liposomes to improve the intestinal bioavailability of curcumin.
2016
This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to inc…
Impaired oral absorption of methylphenidate after Roux-en-Y gastric bypass
2017
The anatomic and physiologic changes in the gastrointestinal (GI) tract after bariatric surgery may significantly affect the pharmacokinetics of medications taken by the patients for various reasons. Unfortunately, there is little information regarding changes in drug absorption after bariatric surgeries, limiting the ability of medical professionals to produce clear recommendations on what changes should be made to the formulations and dosing regimens of drugs after bariatric surgery. In this article, we report and analyze a case of 52-year-old male patient with morbid obesity and attention-deficit/hyperactivity disorder (ADHD) who experienced lack of methylphenidate efficacy after Roux en…