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Chemical Instability (chemical + instability)
Selected AbstractsDynamic Chemical Instabilities in Living Cells May Provide a Novel Route in Drug DevelopmentCHEMBIOCHEM, Issue 10 2004Howard R. Petty Dr. Chemical waves, such as the NAD(P)H (green) and Ca2+(white-orange) waves of neutrophils, are emergent properties of living cells that represent the collective behavior of proteins that constitute intracellular subsystems. Studies of these waves suggest novel approaches in drug development and fresh insights into several clinical issues. [source] Antibody structure, instability, and formulationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2007Wei Wang Abstract The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightforward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1,26, 2007 [source] Microencapsulation of rosmarinic acid using polycaprolactone and various surfactantsINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2010H.-J. Kim Synopsis Rosmarinic acid (RA) has a number of interesting biological activities, e.g. anti-viral, anti-bacterial, anti-inflammatory and antioxidant. The antioxidant activity of RA is stronger than that of vitamin E. Despite its strong antioxidant activity, it was limited to use in cosmetics because of the low water solubility, discolouration and chemical instability. The purpose of this study was to prepare RA-loaded polycaprolactone (PCL) microspheres using emulsion solvent evaporation method and characterize them with different surfactants used in the formation process. Finally, long-term stability of RA was evaluated in the cosmetic formulation. As a result, PCL microspheres were found to be spherical in shape, with zwitterionic surfactant-PCL particles being the smallest size distribution and highest entrapment efficiency of RA. Emulsions containing RA-loaded PCL microspheres showed a better long-term stability of the RA compared with those containing only RA. These results suggest that RA may be stably and efficiently encapsulated into polycaprolactone microspheres. Résumé Micro encapsulation d'acide rosmarinique utilisant la polycaprolactone et divers surfactants L'acide rosmarinique a un certain nombre d'activités biologiques intéressantes, par exemple antivirales, antibactériennes, anti-inflammatoires et antioxydantes. L'activité antioxydante de l'acide rosmarinique est plus puissante que celle de la vitamine E. Malgré sa forte activité antioxydante, son usage en cosmétique est limité en raison de sa faible solubilité dans l'eau, sa décoloration et son instabilité chimique. Le but de cette étude était de préparer des microsphères de PCL chargées d'acide rosmarinique par la méthode d'émulsification par d'évaporation de solvant et de les caractériser selon les différents surfactants utilisés dans le processus de fabrication. Enfin, la stabilitéà long terme de l'acide rosmarinique a étéévaluée dans la formulation cosmétique. Les microsphères PCL ont été trouvé de forme sphérique, avec les surfactants zwitterioniques, les particules PCL offrent une distribution de petites tailles et une efficacité de piégeage en acide rosmarinique la plus élevée. Les émulsions contenant des microsphères PCL chargées d'acide rosmarinique ont montréà long terme une meilleure stabilité en acide rosmarinique que celles contenant l'acide seul. Ces résultats suggèrent que l'acide rosmarinique peut être encapsulé de façon efficace et stable dans des microsphères de polycaprolactone. [source] Synthesis of 2-(5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenamidoethyl-d4 dihydrogen phosphate, tetra-deuterated pAEA,JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 12 2008Kejun Cheng Abstract A labile intermediate phospho-anandamide (2-(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenamidoethyl dihydrogen phosphate, pAEA) has been identified in mouse brain and macrophages, but its precise quantitation was difficult because of its low concentration and chemical instability. We report the synthesis of tetra-deuterated pAEA from 2-aminoethyl dihydrogen phosphate-1,1,2,2-d4 and (5Z,8Z,11Z,14Z)-2,5-dioxopyrrolidin-1-yl icosa-5,8,11,14-tetraenoate. The compound will be used to quantitate the pAEA necessary for a novel biosynthetic pathway. Published in 2008 by John Wiley & Sons, Ltd. [source] Role of thermodynamic, molecular, and kinetic factors in crystallization from the amorphous stateJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Chandan Bhugra Abstract Though there is an advantage in using the higher solubility amorphous state in cases where low solubility limits absorption, physical instability poses a significant barrier limiting its use in solid oral dosage forms. Unlike chemical instability, where useful accelerated stability testing protocols are common, no methodology has been established to predict physical instability. Therefore, an understanding of the factors affecting crystallization from the amorphous state is not only important from a scientific perspective but also has practical applications. Crystallization from the amorphous matrix has been linked to the molecular mobility in the amorphous matrix and recent research has focused on developing the link between these two fundamental properties of glass forming materials. Although researchers have been actively working in this area for some time, there is no current review describing the present state of understanding of crystallization from the amorphous state. The purpose of this review therefore is to examine the roles of different factors such as molecular mobility, thermodynamic factors, and the implication of different processing condition, in crystallization from the amorphous state. We believe an increased understanding of the relative contributions of molecular mobility and processing conditions are vital to increased usage of the amorphous state in solid oral dosage forms. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1329,1349, 2008 [source] Synthesis and Stability in Biological Media of 1H -Imidazole-1-carboxylates of ROS203, an Antagonist of the Histamine H3 ReceptorCHEMISTRY & BIODIVERSITY, Issue 1 2008Mirko Rivara Abstract A series of carbamate derivatives of the H3 antagonist ROS203 (1) were prepared, and their lipophilicity and steric hindrance were modulated by introducing linear or branched alkyl chains of various lengths. In vitro stability studies were conducted to evaluate how structural modulations affect the intrinsic reactivity of the carbamoyl moiety and its recognition by metabolic enzymes. Linear alkyl carbamates were the most susceptible to enzymatic hydrolysis, with bioconversion rates being higher in rat liver and plasma. Chain ramification significantly enhanced the enzymatic stability of the set, with two derivatives (1g and 1h) being more stable by a factor of 8,40 than the ethyl carbamate 1a. Incubation with bovine serum albumin (BSA) showed a protective role of proteins on chemical and porcine-liver esterase (PLE)-catalyzed hydrolysis. Ex vivo binding data after i.v. administration of 1h revealed prolonged displacement of the labeled ligand [3H]-(R)- , -methylhistamine ([3H]RAMHA) from rat-brain cortical membranes, when compared to 1. However, the high rates of bioconversion in liver, as well as the chemical instability of 1h, suggest that further work is needed to optimize the enzymatic and chemical stability of these compounds. [source] | ||||||||||