Impact of the counterion on the solubility and physicochemical properties of salts of carboxylic acid drugs

Aim: Salt formation is a widely used approach to improve the physicochemical and solid state properties of an active pharmaceutical ingredient. In order to better understand the relationships between the active drug, the selected counterion and the resultant salt form, crystalline salts were formed using four different carboxylic acid drugs and a closely related series of amine counterions. Thirty-six related crystalline salts were prepared, characterized and the relationship between solubility and dissolution behaviour and other properties of the salt and the counterion studied. Methods: Salts of four model acid drugs, gemfibrozil, flurbiprofen, ibuprofen and etodolac were prepared using the counterions butylamine, hexylamine, octylamine, benzylamine, cyclohexylamine, tert-butylamine, 2-amino-2-methylpropan-1-ol, 2-amino-2-methylpropan-1,3-diol andtris(hydroxymethyl)aminomethane. Salt formation was confirmed, the salts were characterized and their corresponding solubilities determined and rationalized with respect to the counterions' properties. Results and conclusion: The properties of the salt highly dependent on the nature of the counterion and, although there is considerable variation, some general conclusion can be drawn. For the alkyl amines series, increasing chain length leads to a reduction in solubility across all the acidic drugs studied and a reduction in melting point, thus contradicting simplistic relationships between solubility and melting point. Small, compact counterions consistently produce crystalline salts with high melting point accompanied with a modest improvement in solubility and the nature of hydrogen bonding between the ions has a major impact on the solubility. © 2012 Informa Healthcare USA, Inc.

The pyrolysis of plastics in molten salts

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

The effect of a curing agent on the thermal degradation of fire retardant brominated epoxy resins

The diglycidyl ether of tetrabromobisphenol A, the diglycidyl ether of bisphenol A and their mixture was cured by 4,4'-diaminodiphenyl methane. The pyrolysis of the obtained epoxy resins was studied by TG, DSC, TG/FTIR as well as FTIR characterization of pyrolysis residues. The gaseous and high boiling pyrolysis products were collected, characterized by GC/MS and their formation is discussed. The brominated epoxy resins are thermally less stable than the non-brominated ones. This effect is caused by the amine-containing hardener. The degradation initiation reaction is associated with the formation of hydrogen bromide which further destabilizes the epoxy network. The effect of the curing agent can be used in recycling of epoxy resins to separate brominated pyrolysis products from non-brominated ones.

Supercritical carbonation of calcareous composites:influence of curing

This paper reports the effect of curing on the susceptibility of cementitious composites to carbonation using supercritical carbon dioxide. Samples made using a compression moulding technique were cured in water before and/or after carbonation and the effect on porosity, microstructure, solid phase assemblage and flexural strength was determined. In terms of development of mechanical strength, no benefit was gained from any period of pre- or post-carbonation curing regime. Yet samples cured prior to carbonation underwent minimal chemical reaction between supercritical carbon dioxide and calcium hydroxide, unhydrated cement or C-S-H. Thus there was no correlation between chemical degree of reaction and strength development. The effects responsible for the marked strength gain in supercritically carbonated samples must involve subtle changes in the microstructure of the C-S-H gel, not simple pore filling by calcium carbonate as is often postulated. © 2013 Elsevier Ltd. All rights reserved.\.

Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts

Objectives Understanding the impact of the counterion on the properties of an acidic or basic drug may influence the choice of salt form, especially for less potent drugs with a high drug load per unit dose. The aim of this work was to determine the influence of the hydrogen bonding potential of the counterion on the crystal structure of salts of the poorly soluble, poorly compressible, acidic drug gemfibrozil and to correlate these with mechanical properties. Methods Compacts of the parent drug and the salts were used to determine Young's modulus of elasticity using beam bending tests. Crystal structures were determined previously from X-ray powder diffraction data. Key findings The free acid, tert-butylamine, 2-amino-2-methylpropan-1-ol and 2-amino-2-methylpropan-1, 3-diol salts had a common crystal packing motif of infinite hydrogen-bonded chains with cross-linking between pairs of adjacent chains. The tromethamine (trsi) salt, with different mechanical properties, had a two-dimensional sheet-like network of hydrogen bonds, with slip planes, forming a stiffer compact. Conclusions The type of counter ion is important in determining mechanical properties and could be selected to afford slip and plastic deformation. © 2010 Royal Pharmaceutical Society of Great Britain.

Reactions of nitrilium salts with indole and pyrrole and their derivatives in the synthesis of imines, ketones and secondary amines

I thank SERC for a CASE studentship (to RG. Giles) with the former Fisons Pharmaceuticals division (with Dr. S. C. Eyley) and Dr. B. R. Buckley, of this department, for provided helpful comments on an earlier version of the manuscript.

Reactions of nitrilium salts with indole and pyrrole and their derivatives in the synthesis of imines, ketones and secondary amines

I thank SERC for a CASE studentship (to RG. Giles) with the former Fisons Pharmaceuticals division (with Dr. S. C. Eyley) and Dr. B. R. Buckley, of this department, for provided helpful comments on an earlier version of the manuscript.

Different cation-protonation patterns in mol-ecular salts of unsymmetrical dimethyhydrazine : C2H9N2·Br and C2H9N2·H2PO3

Peer reviewed

Reactions of nitrilium salts with indole and pyrrole and their derivatives in the synthesis of imines, ketones and secondary amines

I thank SERC for a CASE studentship (to RG. Giles) with the former Fisons Pharmaceuticals division (with Dr. S. C. Eyley) and Dr. B. R. Buckley, of this department, for provided helpful comments on an earlier version of the manuscript.

Tailoring Magnetic, Mechanical and Dielectric Properties of Magnetorheological Elastomers based on Natural Rubber and Iron by Magnetic Field Assisted Curing for Possible Applications

If magnetism is universal in nature, magnetic materials are ubiquitous. A life without magnetism is unthinkable and a day without the influence of a magnetic material is unimaginable. They find innumerable applications in the form of many passive and active devices namely, compass, electric motor, generator, microphone, loud speaker, maglev train, magnetic resonance imaging, data recording and reading, hadron collider etc. The list is endless. Such is the influence of magnetism and magnetic materials in ones day to day life. With the advent of nanoscience and nanotechnology, along with the emergence of new areas/fields such as spintronics, multiferroics and magnetic refrigeration, the importance of magnetism is ever increasing and attracting the attention of researchers worldwide. The search for a fluid which exhibits magnetism has been on for quite some time. However nature has not bestowed us with a magnetic fluid and hence it has been the dream of many researchers to synthesize a magnetic fluid which is thought to revolutionize many applications based on magnetism. The discovery of a magnetic fluid by Jacob Rabinow in the year 1952 paved the way for a new branch of Physics/Engineering which later became magnetic fluids. This gave birth to a new class of material called magnetorheological materials. Magnetorheological materials are considered superior to electrorheological materials in that magnetorheology is a contactless operation and often inexpensive.Most of the studies in the past on magnetorheological materials were based on magnetic fluids. Recently the focus has been on the solid state analogue of magnetic fluids which are called Magnetorheological Elastomers (MREs). The very word magnetorheological elastomer implies that the rheological properties of these materials can be altered by the influence of an external applied magnetic field and this process is reversible. If the application of an external magnetic field modifies the viscosity of a magnetic fluid, the effect of external magnetic stimuli on a magnetorheological elastomer is in the modification of its stiffness. They are reversible too. Magnetorheological materials exhibit variable stiffness and find applications in adaptive structures of aerospace, automotive civil and electrical engineering applications. The major advantage of MRE is that the particles are not able to settle with time and hence there is no need of a vessel to hold it. The possibility of hazardous waste leakage is no more with a solid MRE. Moreover, the particles in a solid MRE will not affect the performance and durability of the equipment. Usually MR solids work only in the pre yield region while MR fluids, typically work in the post yield state. The application of an external magnetic field modifies the stiffness constant, shear modulus and loss modulus which are complex quantities. In viscoelastic materials a part of the input energy is stored and released during each cycle and a part is dissipated as heat. The storage modulus G′ represents the capacity of the material to store energy of deformation, which contribute to material stiffness. The loss modulusG′′ represents the ability of the material to dissipate the energy of deformation. Such materials can find applications in the form of adaptive vibration absorbers (ATVAs), stiffness tunable mounts and variable impedance surfaces. MREs are an important material for automobile giants and became the focus of this research for eventual automatic vibration control, sound isolation, brakes, clutches and suspension systems

Resistive Embedded Heating for Homogeneous Curing of Composite Damage Repair

Thesis (Ph.D.)--University of Washington, 2016-08

A petrographic investigation into the durability of common replacement sandstones to the crystallisation of de-icing salts

Scottish sandstone buildings are now suffering the long-term effects of salt-crystallisation damage, owing in part to the repeated deposition of de-icing salts during winter months. The use of de-icing salts is necessary in order to maintain safe road and pavement conditions during cold weather, but their use comes at a price. Sodium chloride (NaCl), which is used as the primary de-icing salt throughout the country, is a salt known to be damaging to sandstone masonry. However, there remains a range of alternative, commercially available de-icing salts. It is unknown however, what effect these salts have on porous building materials, such as sandstone. In order to protect our built heritage against salt-induced decay, it is vital to understand the effects of these different salts on the range of sandstone types that we see within the historic buildings of Scotland. Eleven common types of sandstone were characterised using a suite of methods in order to understand their mineralogy, pore structure and their response to moisture movement, which are vital properties that govern a stone’s response to weathering and decay. Sandstones were then placed through a range of durability tests designed to measure their resistance to various weathering processes. Three salt crystallisation tests were undertaken on the sandstones over a range of 16 to 50 cycles, which tested their durability to NaCl, CaCl2, MgCl2 and a chloride blend salt. Samples were primarily analysed by measuring their dry weight loss after each cycle, visually after each cycle and by other complimentary methods in order to understand their changing response to moisture uptake after salt treatment. Salt crystallisation was identified as the primary mechanism of decay across each salt, with the extent of damage in each sandstone influenced by environmental conditions and pore-grain properties of the stone. Damage recorded in salt crystallisation tests was ultimately caused by the generation of high crystallisation pressures within the confined pore networks of each stone. Stone and test-specific parameters controlled the location and magnitude of damage, with the amount of micro-pores, their spatial distribution, the water absorption coefficient and the drying efficiency of each stone being identified as the most important stone-specific properties influencing salt-induced decay. Strong correlations were found between the dry weight loss of NaCl treated samples and the proportion of pores <1µm in diameter. Crystallisation pressures are known to scale inversely with pore size, while the spatial distribution of these micro-pores is thought to influence the rate, overall extent and type of decay within the stone by concentrating crystallisation pressures in specific regions of the stone. The water absorption determines the total amount of moisture entering into the stone, which represents the total amount of void space for salt crystallisation. The drying parameters on the other hand, ultimately control the distribution of salt crystallisation. Those stones that were characterised by a combination of a high proportion of micro-pores, high water absorption values and slow drying kinetics were shown to be most vulnerable to NaCl-induced decay. CaCl2 and MgCl2 are shown to have similar crystallisation behaviour, forming thin crystalline sheets under low relative humidity and/or high temperature conditions. Distinct differences in their behaviour that are influenced by test specific criteria were identified. The location of MgCl2 crystallisation close to the stone surface, as influenced by prolonged drying under moderate temperature drying conditions, was identified as the main factor that caused substantial dry weight loss in specific stone types. CaCl2 solutions remained unaffected under these conditions and only crystallised under high temperatures. Homogeneous crystallisation of CaCl2 throughout the stone produced greater internal change, with little dry weight loss recorded. NaCl formed distinctive isometric hopper crystals that caused damage through the non-equilibrium growth of salts in trapped regions of the stone. Damage was sustained as granular decay and contour scaling across most stone types. The pore network and hydric properties of the stones continually evolve in response to salt crystallisation, creating a dynamic system whereby the initial, known properties of clean quarried stone will not continually govern the processes of salt crystallisation, nor indeed can they continually predict the behaviour of stone to salt-induced decay.

Betalain rich functional extract with reduced salts and nitrate content from red beetroot (Beta vulgaris L.) using membrane separation technology

An initial laboratory-scale evaluation of separation characteristics of membranes with nominal molecular weight cut-offs (NMWCO) ranging from 30 kD down to 0.5 kD indicated effective separation of betalains in the 0.5 kD region. Subsequent pilot-level trials using 1 kD, loose reverse osmosis (LRO) and reverse osmosis (RO) spiral-wound membranes showed LRO membrane to be very efficient with up to 96% salt and 47% other dissolved solids removed while retaining majority of the pigment (∼98%) in the betalain rich extract (BRE). The total betalain content in the BRE increased up to 46%, the highest recovery reported so far at pilot scale level. Interestingly, more than 95% of the nitrates were removed from the BRE after the three diafiltrations. These studies indicate that membrane technology is the most efficient technique to produce BRE with highly reduced amounts of salts and nitrate content.

A contribution towards the performance and structural understanding of copper and nickel salts as ammonia stores

The ongoing depletion of fossil fuels and the severe consequences of the greenhouse effect make the development of alternative energy systems crucially important. While hydrogen is, in principle, a promising alternative, releasing nothing but energy and pure water. Hydrogen storage is complicated and no completely viable technique has been proposed so far. This work is concerned with the study of one potential alternative to pure hydrogen: ammonia, and more specifically its storage in solids. Ammonia, NH3, can be regarded as a chemical hydrogen carrier with the advantages of strongly reduced flammability and explosiveness as compared to hydrogen. Furthermore, ammine metal salts presented here as promising ammonia stores easily store up to 50 wt.-% ammonia, giving them a volumetric energy density comparable to natural gas. The model system NiX2–NH3 ( X = Cl, Br, I) is studied thoroughly with respect to ammine salt formation, thermal decomposition, air stability and structural effects. The system CuX2–NH3 ( X = Cl, Br) has an adverse thermal decomposition behaviour, making it impractical for use as an ammonia store. This system is, however, most interesting from a structural point of view and some work concerning the study of the structural behaviour of this system is presented. Finally, close chemical relatives to the metal ammine halides, the metal ammine nitrates are studied. They exhibit interesting anion arrangements, which is an impressive showcase for the combination of diffraction and spectroscopic information. The characterisation techniques in this thesis range from powder diffraction over single crystal diffraction, spectroscopy, computational modelling, thermal analyses to gravimetric uptake experiments. Further highlights are the structure solutions and refinements from powder data of (NH4)2[NiCl4(H2O)(NH3)] and Ni(NH3)2(NO3)2, the combination of crystallographic and chemical information for the elucidation of the (NH4)2[NiCl4(H2O)(NH3)] formation reaction and the growth of single crystals under ammonia flow, a technique allowing the first documented successful growth and single crystal diffraction measurement for [Cu(NH3)6]Cl2.

Chromatographic determination of fatty acids profiles in regionally-produced Portuguese goat cheese along curing

The biochemistry of cheese ripening involves mechanisms such as glycolysis, proteolysis and lipolysis. Fatty acids are released by the action of lipases from different sources, milk, rennet, bacteria, moulds included as secondary starters, and other exogenous lipases, during lipolysis [1]. The composition of the lipid fraction contributes positively to the flavour of cheese, for being precursors of more complex aroma compounds responsible for the characteristic “goaty flavour” of goat cheeses [2]. Goat milk is recognized by its easier digestibility, alkalinity, buffering capacity and certain therapeutic values in medicine and human nutrition [3]. A high total content of fatty acids is strongly linked to a rancid and tart off flavour in goat milk and may be considered undesirable in most cheese varieties [4]. In this sense, the purpose of the present study was to examine the composition and changes in fatty acids and saponification value of goat cheese during curing period (2, 7 and 12 months). Goat cheese was made in industrial unit of Cachão - Mirandela (Trás-os- Montes) with raw milk Serrana goats’ race, salt and rennet from animal origin. During the first two months, the samples were stored in a ripening chamber (9.5-11 °C and RH 75-85%). From the second month to one year, the samples were stored in a preservation chamber (10.5-12 °C and RH 75-85%). The fatty acids profile of the inner part of the cheese was analyzed by gas-chromatography coupled to flame ionization detection (GC-FID). The degree of saponification was determined both in the crust and inside the cheese by HCl titration of ethanol KOH solution of the samples. Twenty-six fatty acids (FA) were identified and quantified in the inner part of the cheese (total fat was 45-46 g/100 g during the curing period). Saturated fatty acids (SFA) did not change up to 7 months of curing, increasing only after 12 months, being palmitic (C16:0), stearic (C18:0), myristic (C14:0) and capric (C10:0) acids the most abundant FA in this class. Monounsaturated fatty acids (MUFA) decreased only after 12 months, and oleic acid (C18:1) was the predominant FA. In polyunsaturated fatty acids (PUFA) class, the most abundant were linoleic (C18:2) and linolenic (C18:3) acids, and followed the same tendency of MUFA. This is corroborated by an increase in the degree of saponification, either in the crust as in the inner part of the cheese, after 12 months of curing, probably related with the saturation of the fatty acids [3]. Extra-long curing can be done in cheeses produced with goat milk up to seven months of storage without changing the total fat and individual FA content.