Search results for "DISCOVERY"

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…

Hierarchical Mass Transfer Analysis of Drug Particle Dissolution, Highlighting the Hydrodynamics, pH, Particle Size, and Buffer Effects for the Disso…

2020

Dissolution is a crucial process for the oral delivery of drug products. Before being absorbed through epithelial cell membranes to reach the systemic circulation, drugs must first dissolve in the human gastrointestinal (GI) tract. In vivo and in vitro dissolutions are complex because of their dependency upon the drug physicochemical properties, drug product, and GI physiological properties. However, an understanding of this process is critical for the development of robust drug products. To enhance our understanding of in vivo and in vitro dissolutions, a hierarchical mass transfer (HMT) model was developed that considers the drug properties, GI fluid properties, and fluid hydrodynamics. T…

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…

Chemists and Physicists searching for element 43

2005

Prediction of acute toxicity of organophosphorus pesticides using topological indices

2007

Topological indices were used in the prediction of the acute toxicity (intraperitoneal and oral LD(50)) of organophosphorus pesticides on rats. Models with six variables for the prediction of LD(50)-i.p. (r = 0.849, Q(2) = 0.613) and eight variables for LD(50)-oral (r = 0.906, Q(2) = 0.701) were selected. External group and cross-validation by use of leave-n-out tests were also performed in order to assess the stability and the prediction performance of the selected topological models.

‘One-Pot’ Synthesis of Raumacline from Ajmaline

1993

For the alkaloid raumacline (2), which is a biotransformation product of ajmaline (1) in Rauwolfia serpentina cell cultures, an efficient ‘one-pot’ synthesis was developed using a NaBH4/riboflavin/light-mediated transformation of 1 into 2 with a total yield of 86%.

Substituent effect on the redox potential of substituted (aryl)(2-nitrobenzo[ b ]thiophen-3-yl)amines

2001

Abstract The electronic effect of some meta- or para-substituents on the reduction of the title compounds has been investigated. The reversible reduction potential values of these compounds have been evaluated by cyclic voltammetry at a mercury electrode in 0.1 M tetraethylammoniumtetrafluoroborate, dimethylsulfoxide solutions. The substituent effect depends on both its nature and its position. The reduction potential values of the derivatives studied have been correlated with the Hammett substituent constants.

Mechanistic and kinetic insight into spontaneous cocrystallisation of isoniazid and benzoic acid

2015

Solid-state cocrystallisation is of contemporary interest, because it offers an easy and efficient way to produce cocrystals, which are recognized as prospective pharmaceutical materials. Research explaining solid-state cocrystallisation mechanisms is important, but still too scarce to give a broad understanding of factors governing and limiting these reactions. Here we report an investigation of the mechanism and kinetics of isoniazid cocrystallisation with benzoic acid. This reaction is spontaneous; however its rate is greatly influenced by environmental conditions (humidity and temperature) and pre-treatment (milling) of the sample. The acceleration of cocrystallisation in the presence o…

Synthesis and 1H-NMR configurational study of δ3-thiazolines from 2-aza-1,3-dienes

1992

Abstract A [4+1] heterocyclization process involving 2-aza-1,3-dienes and elemental sulphur leading to the synthesis of Δ3-thiazolines with excellent yields is described. A 1D TOCSY and 1D NOESY study of these systems was made in order to establish the configurations of the diastereoisomeric mixture.

Dendrimers with peripheral stilbene chromophores

2006

Abstract Two types of dendritic nanoparticles were prepared, which contain ( E )-stilbene chromophores in the terminal positions of the dendrons. The compounds showed a highly efficient photoreactivity in the course of which statistical CC bond formations led to a crosslinking of the particles. Finally, all stilbene chromophores reacted and the typical ( E )-stilbene absorption and fluorescence disappeared completely.