The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
STEPHEN ROBERT BYRN - One of the best experts on this subject based on the ideXlab platform.
-
solid state investigations of <B>ErythromycinB> a dihydrate structure nmr spectroscopy and hygroscopicity
Journal of Pharmaceutical Sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
-
Solid‐state investigations of <B>ErythromycinB> a dihydrate: Structure, NMR spectroscopy, and hygroscopicity
Journal of pharmaceutical sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
Gregory A Stephensonx - One of the best experts on this subject based on the ideXlab platform.
-
solid state investigations of <B>ErythromycinB> a dihydrate structure nmr spectroscopy and hygroscopicity
Journal of Pharmaceutical Sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
-
Solid‐state investigations of <B>ErythromycinB> a dihydrate: Structure, NMR spectroscopy, and hygroscopicity
Journal of pharmaceutical sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
Jill Barber - One of the best experts on this subject based on the ideXlab platform.
-
enhancement of the properties of a drug By mono deuteriation reduction of acid catalysed formation of a gut motilide enol ether from 8 deuterio <B>ErythromycinB> B
Organic and Biomolecular Chemistry, 2016Co-Authors: Pranab K Bhadra, Abdolreza Hassanzadeh, Gareth A. Morris, Biljana Arsic, D G Allison, Jill BarberAbstract:<B>ErythromycinB> B is structurally very similar to <B>ErythromycinB> A, and also shares its clinically important antiBacterial activity. Its potential advantage is that it is much more staBle to acid. Both compounds are susceptiBle to 6–9-enol ether formation, involving loss of a proton from C-8. The enol ethers lack antiBacterial activity and can give rise to unpleasant gut motilide side-effects. Our previous work on degradation kinetics revealed that the formation of <B>ErythromycinB> B enol ether from <B>ErythromycinB> B is suBject to a large deuterium isotope effect. We therefore synthesized 8-d-<B>ErythromycinB> B (in 87% yield) in the hope that acid-catalysed enol ether formation would Be reduced, relative to <B>ErythromycinB> B. In a range of microBiological and Biochemical assays, deuteriation did not appear to compromise the efficacy of the drug. Degradation studies showed, however, that incorporation of deuterium into <B>ErythromycinB> B reduces (though does not completely suppress) enol ether formation, providing the possiBility of using a facile mono-deuteriation to reduce the gut motilide side-effects of the drug.
-
<B>ErythromycinB> B: conformational analysis and antiBacterial activity
MedChemComm, 2011Co-Authors: Paul Tyson, Abdolreza Hassanzadeh, Mohd Nizam Mordi, David G. Allison, Viter Márquez, Jill BarberAbstract:<B>ErythromycinB> B, an acid-staBle co-metaBolite of the important antiBiotic <B>ErythromycinB> A, differs from <B>ErythromycinB> A only in the aBsence of a hydroxyl group at C12, yet it has never Been licensed for clinical use. We descriBe an NMR-Based analysis of the conformation of <B>ErythromycinB> B, Both free in aqueous solution and when weakly Bound to Bacterial riBosomes and show that it is conformationally similar to <B>ErythromycinB> A. The antiBacterial activity of <B>ErythromycinB> B is shown to Be similar to that of <B>ErythromycinB> A, But after acid-treatment, resemBling exposure to the stomach, <B>ErythromycinB> B suBstantially retains antiBacterial activity, whereas <B>ErythromycinB> A does not.
-
Pediatric <B>ErythromycinB>s: a comparison of the properties of <B>ErythromycinB>s A and B 2'-ethyl succinates.
Journal of Medicinal Chemistry, 2006Co-Authors: Abdolreza Hassanzadeh, Peter A. Gorry, Gareth A. Morris, Jill BarberAbstract:The antiBiotic <B>ErythromycinB> A is generally administered to children as a suspension of the pro-drug <B>ErythromycinB> A 2‘-ethyl succinate. The success of the pro-drug depends on (a) elimination of the unacceptaBly Bitter taste of free <B>ErythromycinB>, (B) its staBility against stomach acid, and (c) its smooth (Base-catalyzed) hydrolysis in the Body to yield active <B>ErythromycinB>. We have investigated the rates and pathways of acid-catalyzed degradation and Base-catalyzed hydrolysis of the 2‘-ethyl succinates of <B>ErythromycinB>s A and B. Esterification does not protect the drugs against acid-catalyzed degradation in solution; however, <B>ErythromycinB> B 2‘-ethyl succinate is much more staBle than the corresponding <B>ErythromycinB> A ester, degrading nearly 40 times more slowly. The rates of Base-catalyzed hydrolysis in conditions mimicking the Blood stream are similar for the two pro-drugs. We conclude that <B>ErythromycinB> B 2‘-ethyl succinate is an attractive prospect as a pediatric <B>ErythromycinB> pro-drug.
-
Design, synthesis, and evaluation of staBle and taste-free <B>ErythromycinB> proprodrugs.
Journal of medicinal chemistry, 2005Co-Authors: Pranab K Bhadra, Gareth A. Morris, Jill BarberAbstract:<B>ErythromycinB> A is normally formulated for children as its 2'-ethyl succinate, a taste-free prodrug. Unfortunately, the prodrug hydrolyzes at a measuraBle rate in the medicine Bottle, leading to the vile-tasting <B>ErythromycinB>. We have prepared derivatives of <B>ErythromycinB> B as putative paediatric prodrugs, taking advantage of the much improved acid staBility of <B>ErythromycinB> B relative to <B>ErythromycinB> A. Thus, <B>ErythromycinB> B enol ether ethyl succinate is very poorly soluBle in water, and its hydrolysis is undetectaBle in conditions resemBling the medicine Bottle. In acid, however, it converts rapidly to <B>ErythromycinB> B 2'-ethyl succinate, and this is in turn hydrolyzed to <B>ErythromycinB> B in neutral and Basic conditions. Derivatives of <B>ErythromycinB> B enol ether are therefore proposed as taste-free proprodrugs of <B>ErythromycinB> B.
-
Acid-catalyzed degradation of clarithromycin and <B>ErythromycinB> B: a comparative study using NMR spectroscopy.
Journal of medicinal chemistry, 2000Co-Authors: Mohd Nizam Mordi, Gareth A. Morris, Michelle D. Pelta, Valerie Boote, Jill BarberAbstract:One of the major drawBacks in the use of the antiBiotic <B>ErythromycinB> A is its extreme acid sensitivity, leading to degradation in the stomach following oral administration. The modern derivative clarithromycin degrades By a different mechanism and much more slowly. We have studied the pathway and kinetics of the acid-catalyzed degradation of clarithromycin and of <B>ErythromycinB> B, a Biosynthetic precursor of <B>ErythromycinB> A which also has good antiBacterial activity, using 1H NMR spectroscopy. Both drugs degrade By loss of the cladinose sugar ring and with similar rates of reaction. These results suggest that <B>ErythromycinB> B has potential as an independent therapeutic entity, with superior acid staBility compared with <B>ErythromycinB> A and with the advantage over clarithromycin of Being a natural product.
Oseph G Stowell - One of the best experts on this subject based on the ideXlab platform.
-
solid state investigations of <B>ErythromycinB> a dihydrate structure nmr spectroscopy and hygroscopicity
Journal of Pharmaceutical Sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
-
Solid‐state investigations of <B>ErythromycinB> a dihydrate: Structure, NMR spectroscopy, and hygroscopicity
Journal of pharmaceutical sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
Pascal H Toma - One of the best experts on this subject based on the ideXlab platform.
-
solid state investigations of <B>ErythromycinB> a dihydrate structure nmr spectroscopy and hygroscopicity
Journal of Pharmaceutical Sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.
-
Solid‐state investigations of <B>ErythromycinB> a dihydrate: Structure, NMR spectroscopy, and hygroscopicity
Journal of pharmaceutical sciences, 1997Co-Authors: Gregory A Stephensonx, Oseph G Stowell, Pascal H Toma, Ralph R Pfeiffer, STEPHEN ROBERT BYRNAbstract:The crystal structures of the commercially availaBle form of <B>ErythromycinB> A dihydrate and clarithromycin anhydrate, in addition to the structure of <B>ErythromycinB> B dihydrate, are reported in this paper. In light of the crystallographic data, analysis of the structural information provides insight into the physical properties of these pharmaceuticals. The propensity of these pharmaceuticals to form solvated structures is discussed and the hygroscopicity of <B>ErythromycinB> A dihydrate is investigated. Solid-state 13C NMR was used to monitor changes that occur when the dihydrate form of <B>ErythromycinB> A is stored under conditions of low relative humidity. Although <B>ErythromycinB> A dihydrate retains its crystallographic order at low humidity, as indicated By its X-ray powder diffraction pattern, the local chemical environment is dramatically influenced By the loss of the water molecules and results in dramatic changes in its solid-state 13C NMR spectrum.