Search results for "Lability"
showing 10 items of 802 documents
Study of the cytotoxic activity of beauvericin and fusaproliferin and bioavailability in vitro on Caco-2 cells.
2010
Abstract Beauvericin (BEA) is a cyclohexadepsipeptide mycotoxin which has insecticidal properties and produces cytotoxic effects in mammalian cells. Fusaproliferin (FUS) is a mycotoxin that has toxic activity against brine shrimp, insect cells, and teratogenic effects on chicken embryos. The aim of this study was to determine the cytotoxicity of BEA and FUS in human epithelial colorectal adenocarcinoma HT-29 and Caco-2 cells, the transepithelial transport and the bioavailability using Caco-2 cells as a simulated in vitro gastrointestinal model of the human intestinal epithelium. The inhibitory concentration (IC 50 ) evidenced by BEA in the Caco-2 cells was 24.6 and 12.7 μM at 24 and 48 h ex…
Model and optimal Call Admission Policy in Cellular Mobile Networks
2000
For current cellular networks, two important Quality of Service (QoS) measures are the fractions of new and handoff calls that are blocked due to unavailability of channels. Based on these QoS measures, we propose a queuing network model with impatient users for handoff and new calls in cellular mobile networks. The number of simultaneous calls, that can be supported, is modeled by C identical servers with exponentially distributed session duration for each one of them. Priority is given to handoffs over new calls. We use for that a Guard Channel policy that reserves a set of CH channels for handoff calls, new calls being served at their arrival if there are more than CH available channels.…
A joint action of deep eutectic solvents and ultrasound to promote Diels−Alder reaction in a sustainable way
2020
The need to reduce environmental impact of chemical processes has induced a surge of attention in the choice of solvent and methodologies to carry them out. In this context, we studied the Diels−Alder reaction using N-ethylmaleimide as dienophile and changing the nature of the diene in deep eutectic solvents (DES) under both conventional heating and ultrasonic activation. DES obtained by the combination of different hydrogen bond acceptors and donors allowed assessing the role played by solvent nature. DES proved suitable solvent media for the target reaction, allowing higher yields and faster reactions compared to conventional organic solvents. The trend of yields, both in silent and under…
Toward Biopredictive Dissolution for Enteric Coated Dosage Forms
2016
The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions. Two commercially available enteric-coated aspirin products were used as model formulations (Aspirin Protect 300 mg, and Walgreens Aspirin 325 mg). The disintegration performance of these products in a physiological 8 mM pH 6.5 bicarbonate buffer (representing the conditions in the proximal small intestine) was used as a standard to optimize the employed phosphate buffer molarity. To account for the fact that a pH and buffer molarity gradient exists along the small intestine, the introduction of such a gradient was proposed for p…
In vivo models and decision trees for formulation development in early drug development: A review of current practices and recommendations for biopha…
2018
The ability to predict new chemical entity performance using in vivo animal models has been under investigation for more than two decades. Pharmaceutical companies use their own strategies to make decisions on the most appropriate formulation starting early in development. In this paper the biopharmaceutical decision trees available in four EFPIA partners (Bayer, Boehringer Ingelheim, Bristol Meyers Squibb and Janssen) were discussed by 7 companies of which 4 had no decision tree currently defined. The strengths, weaknesses and opportunities for improvement are discussed for each decision tree. Both pharmacokineticists and preformulation scientists at the drug discovery & development interf…
Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets.
2017
Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was meas…
Activity–Bioavailability balance in Oral Drug Development for a Selected Group of 6‐Fluoroquinolones
2002
Abstract A nomogram is proposed to select the best candidate in drug development studies with quinolones and is intended to substitute other possible models. The nomogram is referred to as an activity–bioavailability balance (ABB) because it includes the following two criteria: ABB= 1 / gm MIC ( drug candidate ) 1 /gm MIC ( ciprofloxacin ) · F calc \( drug candidate \) F calc ( ciproflaxacin ) . The in vitro activity of a group of 4′ N ‐alkyl‐ciprofloxacin derivatives was determined together with that of ciprofloxacin, initially against some reference strains and subsequently against 159 clinical isolates of eight selected species. The inverse of the geometric mean of the lowest concentrati…
Does the addition of caseinophosphopeptides or milk improve zinc in vitro bioavailability in fruit beverages?
2009
Abstract The influence of caseinophosphopeptides (CPPs) added to fruit beverage versus milk based fruit beverage upon zinc retention, transport, and uptake, as well as the influence of Fe supplementation, were studied using a combined simulated gastrointestinal digestion/Caco-2 cell system. Zinc retention, transport, and uptake of milk based fruit beverage was 4- to 5-fold greater than that of fruit beverages with or without CPPs – no statistically significant differences being observed in relation to the presence or absence of CPPs. Possibly, a slow release of CPPs throughout the digestive tract, as can be expected to take place during the digestion of casein, has a more beneficial effect …
Availability of polyphenols in fruit beverages subjected to in vitro gastrointestinal digestion and their effects on proliferation, cell-cycle and ap…
2009
Abstract Three fruit beverages: Fb (grape–orange–apricot), FbFe (Fb + iron sulphate) and FbFeM (FbFe + skimmed milk) were subjected to in vitro gastrointestinal digestion. Addition of Fe and milk decreased the phenolic content of Fb by 13% and 55%, respectively. The digestion process decreased the phenolic content by 47%, 60%, and 70% in Fb, FbFe and FbFeM with respect to the initial, non-digested, Fb. Caco-2 cells were incubated for 4 h daily for four days or continuously for 24 h with bioaccessible fractions obtained after the digestion (digests). Polyphenols were not metabolised by Caco-2 cells. Fb digest (∼50 μM total phenolics) was the sample that led to the highest inhibition of cell …