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Biomedical subjects

A G Mitchell

Publications and source records attributed to A G Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1985

Polymorphism in metoclopramide hydrochloride and metoclopramide.

Metoclopramide hydrochloride (MCPHCl.H2O) and metoclopramide base (MCP) have been studied by DSC, thermomicroscopy, X-ray diffraction and infrared spectroscopy. MCPHCl.H2O does not readily lose water of crystallization either from the solid state or from the melt, but depending on the conditions, dehydration can give rise to two anhydrous polymorphs, MCPHCl/Form I (mp 187 degrees C) and MCPHCL/Form II (mp 155 degrees C). Form I crystallizes from the melt of Form II and not by a reversible solid-solid transition. The anhydrous hydrochloride therefore shows monotropic polymorphism where Form I is the stable polymorph and Form II, a metastable polymorph. Thermal analysis of MCP shows that the base exists as two enantiotropic polymorphs. The transition of the form stable at room temperature (MCP/Form I) to the form stable at high temperatures (MCP/Form II mp 147 degrees C) occurs extremely rapidly at 125 degrees C but the reverse process requires one month at room temperature (approximately equal to 22 degrees C). It is therefore possible to compare the X-ray diffraction powder patterns and infrared spectra of MCP Forms I and II.

Calorimetry, Differential Scanning↗
PubMed1984

Precipitation of calcium gluceptate from aqueous solutions.

A precipitate encountered in solutions of calcium gluceptate was identified as hydrated calcium gluceptate. Precipitation was associated with a change from a very soluble amorphous anhydrous form to a sparingly soluble crystalline hydrate, the presence of seed crystals inducing crystallization, and unsuitable proportions of the alpha- and beta-epimers of calcium gluceptate. Various commercial samples and the corresponding precipitates were examined by elemental analysis, thermal analysis, X-ray diffraction, IR spectroscopy, and GC-MS. The proportion of the alpha- and beta-epimers in commercial samples was quantitated by GC. In this method, an aqueous solution of calcium gluceptate was converted into a mixture of glucoheptonic acids and their corresponding lactones by passage through a cation-exchange resin. The solution was freeze-dried, the acid-lactone mixture converted to the gamma-lactones using concentrated hydrochloric acid, and the resulting material trimethylsilylated with trimethylsilylimidazole. Stability studies of solutions prepared from calcium gluceptate obtained from various commercial sources indicate that above approximately 50% alpha-epimer, stability decreased with an increase in the relative proportion of the alpha-epimer. Material complying with USP specifications (pure alpha-epimer) is the least stable in solution. It is suggested that calcium gluceptate containing approximately equal proportions of the alpha- and beta-epimers be introduced in the USP monograph together with a method for estimating the proportions of the epimers.

Chemical Phenomena↗
PubMed1984

The preparation and characterization of ferrous sulphate hydrates.

Ferrous sulphate BP, FeSO4,7H2O, dehydrates to form FeSO4,4H2O when the relative humidity (RH) is less than 65%, or on heating at 40 degrees C. The tetrahydrate was also prepared by recrystallization at 60 degrees C from aqeuous solutions of the sulphate. Commercial dried ferrous sulphate BP is FeSO4,H2O but the method of preparation given in the BP produces FeSO4,4H2O which is the stable form at RH less than 65% (25 degrees C). A crystalline monohydrate was prepared either by heating the tetrahydrate on a boiling water bath to constant weight or heating the heptahydrate under vacuum at 60 degrees C in the presence of water vapour evolved from the water of crystallization. An X-ray amorphous form of FeSO4,H2O was made by heating the heptahydrate at 100 degrees C under vacuum with the removal of water vapour. Crystalline FeSO4,H2O rehydrates to the heptahydrate when RH greater than 65% but the amorphous form recrystallizes as the stable tetrahydrate at RH greater than 0 and less than 65%. The various hydrates were characterized by DSC and X-ray diffraction. A simple procedure is described for obtaining data to construct a RH-composition phase diagram. The method combines measurement of any weight changes of each hydrate after storage at various controlled humidities together with a direct measurement of RH over the hydrate pairs. The thermal dehydration pathways are reported together with the RH-composition phase diagrams.

Chemistry, Pharmaceutical↗
PubMed1979

Angina, aortic stenosis and coronary heart disease.

The pre-operative clinical and haemodynamic findings of 139 consecutive patients with aortic stenosis were analysed in an attempt to determine the incidence and influence of coronary heart disease on the mode of presentation of patients with aortic stenosis. The overall incidence of coronary heart disease was 32%. 105 patients (76%) presented with angina and of these, 41 patients (39%) had significant coronary heart disease as compared to 4 (13%) of the remaining 34 patients who did not present with angina. Clinical parameters including age, sex, severity of angina together with the presence of associated symptoms and precipitating factors were unhelpful in distinguishing those patients with coronary heart disease. Evidence of previous transmural myocardial infarction or the presence of ST-T abnormalities in the absence of digitalis and the changes of left ventricular hypertrophy were reliable electrocardiographic signs of coronary heart disease. Although peak systolic aortic valve gradient tended to decrease with increasing severity of coronary heart disease, the severity of aortic stenosis was not a reliable indicator of the presence of coronary disease. Patients with coronary heart disease in the absence of angina all had a combination of moderate aortic stenosis and single vessel disease. It is concluded that coronary heart disease cannot be predicted in patients with angina and, in the absence of angina occurs with an incidence sufficiently high to advocate the use of coronary angiography as part of the investigation of all patients with aortic stenosis being considered for valve replacement.

Adult↗
PubMed1978

Preservation of solubilized and emulsified systems I: Correlation of mathematically predicted preservative availability with antimicrobial activity.

Mathematical models were investigated for the distribution and antimicrobial activity of chlorocresol in solubilized and emulsified systems stabilized with a nonionic surfactant. The concentration of free preservative in the solubilized systems was described adequately by an equation widely used to describe the binding of small molecules to macromolecules. For the emulsions, this equation was combined with an expression for the partitioning of the preservative between the oil and water phases. It was confirmed that short-term antimicrobial activity can be related to the free (unbound) preservative concentration in the aqueous phase and that preservative solubilized within the surfactant micelles or partitioned into the oil phase does not contribute to short-term preservation.

Bacteria↗
PubMed1978

Preservation of solubilized and emulsified systems II: Theoretical development of capacity and its role in antimicrobial activity of chlorocresol in cetomacrogol-stabilized systems.

The preservation of solublized and emulsified disperse systems against microbial spoilage depends on the free (unbound) preservative concentration in the aqueous phase and the capacity of the system. The capacity may be defined as the system's ability to resist losses in free preservative concentration. The theory of capacity is developed quantitatively for solubilized and emulsified systems containing the preservative chlorocresol stabilized by the nonionic surfactant cetomacrogol. Equations are derived for solubilized systems that relate capacity to surfactant concentration and the interaction between the surfactant and the preservative. Additional terms are included in the equations to account for the effects of the oil phase on the capacity of oil-in-water emulsions.

Bacteria↗