A Correlation between the Dynamic Viscosity and Crystallisation of Felodipine from its Amorphous Polymer Solid Dispersion

Purpose Previously, it has been reported that molecular mobility determines the rate of molecular approach to crystal surfaces, while entropy relates to the probability of that approaching molecule having the desirable configuration for further growth of the existing crystal; and the free energy dictates the probability of that molecule not returning to the liquid phase1. If we plot the crystal growth rate and viscosity of a supercooled liquid in a log-log format, the relationship between the two is linear, indicating the influence viscosity has upon crystal growth rate. However, such approximation has been derived from pure drug compounds and it is apparent that further understanding of crystallization from drug-polymer solid dispersion is required in order to stabilise drugs embedded within amorphous polymeric solid dispersions. Methods Mixtures of felodipine and polymer (HPMCAS-HF, PVPK15 and Soluplus®) at specified compositions were prepared using a Restch MM200 ball mill. To examine crystal growth within amorphous solid dispersions, samples were prepared by melting 5-10 mg of ball milled mixture at 150°C for 3-5 minutes on a glass slip pre-cleaned with methanol and acetone. All prepared samples were confirmed to be crystal free by visual observation using a polarised light microscope (Olympus BX50). Prepared samples were stored at 0% RH (P2O5), inside desiccators, maintained in ovens at 80°C. For the dynamic viscosity measurement, approximately 100-200mg ball milled mixture was heated on the base plate of a rotational rheometer at 150°C for 5 minutes and the top plate was lowered to a defined gap to form a good contact with the material. The sandwiched amorphous material was heated to 80°C and the viscosity was measured. Results The equation was used to probe the correlation of viscosity to crystal growth rate. In comparison to the value of xi in log-log equation reported from pure drug compound, a value of 1.63 was obtained for FD-polymer solid dispersions irrespective of the polymer involved. &#8733 Conclusion The high xi value suggests stronger viscosity dependence may exist for amorphous FD once incorporated with amorphous polymer.

Ionic liquid gel materials: applications in green and sustainable chemistry

Ionic liquid gel materials offer a way to further utilise ionic liquids in technological applications. Combining the controlled and directed assembly of gels, with the diverse applications of ionic liquids, enables the design of a heady combination of functional tailored materials, leading to the development of task specific / functional ionic liquid gels. This review introduces gels and gel classification, focusing on ionic liquid gels and their potential roles in a more sustainable future. Ionic liquid gels provide the ability to build functionality at every level, the solid component, the ionic liquid, and any incorporated active functional agents. This allows materials to be custom designed for a vast assortment of applications. This diverse class of materials has the potential to yield functional materials for green and sustainable chemistry, energy, electronics, medicine, food, cosmetics, and more. The discussion of the development of ionic liquid gel materials for applications in green and sustainable chemistry centres on uses of ionic liquid gels in catalysis and energy.

Studies into the effect of temperature on the impact of model particles in co-melt granulation

In co-melt granulation, collisions occur between the particles to be agglomerated and the binder material. Depending on the stage of granulation, the binder material can be in the solid or liquid phase. The outcome of these collisions controls the dynamics of the granulation process and the fundamental physics of the impacts are of interest. This paper examines the impact of glass beads (model particles) and solid Poly Ethylene Glycol (PEG) flakes on a substrate of PEG as the temperature of the PEG layer is increased from below its melting point to above it. While the layer is in the solid state, the result of the impact can be quantified by the coefficient of restitution. When the layer is in the liquid state, the impact can be quantified by the immersion behaviour. The results obtained show that the coefficient of restitution between either glass beads and PEG flakes and the PEG layer is strongly affected by temperatures. As the PEG layer approaches its melting point, the coefficient of restitution falls to zero. Once the temperature of the PEG layer exceeds the melting point, the impact is characterised by a transient maximum indentation and then rebound to an equilibrium position. These too are strongly dependent on temperature.

Gas liquid equilibria at high pressures

Este trabalho tem como objectivo a medição da solubilidade de gases em líquidos a altas pressões. Para a realização experimental foi usada uma célula de altas pressões de volume variável e um método de observação directa para a detecção das transições de fase. As condições usadas neste trabalho experimental foram temperaturas entre 276.00 e 373.15 K e pressões ate 100 MPa. Numa primeira fase foram efectuadas medições de solubilidade de metano em anilina pura e para uma solução aquosa de composição mássica igual a 5% em anilina. A anilina é fundamentalmente usada em processos como a produção de borracha, de poliuretanos, pigmentos e tintas, fármacos, herbicidas e fungicidas. É usualmente produzida através de processos de redução do nitrobenzeno por reacção com o HCl. De facto, esta síntese é um processo químico complexo onde um grande número de processos compete entre si. Alterações nas condições do processo com a possível formação de produtos intermediários podem afectar a eficiência do processo. Para a sua melhoria foi sugerido que o hidrogénio usado fosse simultaneamente produzido e gasto no reactor principal. Neste caso e para a produção do mesmo, era necessário adicionar metano e água ao reactor. Tendo por base a ideia de que as reacções onde o hidrogénio é reagente e produto ocorrem em simultâneo, torna-se clara a importância do estudo da solubilidade do metano em anilina pura e em soluções aquosas desta. Numa segunda fase foi estudada a solubilidade do dióxido de carbono em soluções aquosas de tri-iso-butil(metil)fosfónio tosilato, com composições molares são de 4, 8 e 12% em líquido iónico. Este pertencente à família dos fosfónios. Possui uma viscosidade e densidade elevadas, é térmica e quimicamente estável e ainda possui uma elevada polaridade. Apresenta uma miscibilidade completa em água e nos solventes mais usuais, como o diclorometano e tolueno, não sendo no entanto míscivel em hexano. O tri-isobutil( metil)fosfónium tosilato é usado como solvente nos processos de hidroformilação de olefinas e ainda em processos de captura e conversão de dióxido de carbono. Neste trabalho experimental, a temperatura e a pressão foram inicialmente aumentadas até o sistema atingir o equilíbrio. A pressão é diminuída lentamente até se verificar o aparecimento/desaparecimento da última bolha de gás. A pressão à qual a última bolha de gás desaparece representa a pressão de equilíbrio para aquela temperatura. Este procedimento foi efectuado para vários sistemas e várias temperaturas.

DRIFT and DRUV spectroscopy methods for studying the interaction of metal compounds with native cellulose

Dissertação de mestrado, Qualidade em Análises, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Enantiomeric fraction evaluation of pharmaceuticals in environmentalmatrices by liquid chromatography-tandem mass spectrometry

The interest for environmental fate assessment of chiral pharmaceuticals is increasing and enantioselective analytical methods are mandatory. This study presents an enantioselective analytical method for the quantification of seven pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected chiral pharmaceuticals belong to three different therapeutic classes, namely selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol, propranolol) and a beta2-adrenergic agonist (salbutamol). The analytical method was based on solid phase extraction followed by liquid chromatography tandem mass spectrometry with a triple quadrupole analyser. Briefly, Oasis® MCX cartridges were used to preconcentrate 250 mL of water samples and the reconstituted extracts were analysed with a Chirobiotic™ V under reversed mode. The effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was used to validate the method. Linearity (r2 > 0.99), selectivity and sensitivity were achieved in the range of 20–400 ng L−1 for all enantiomers, except for norfluoxetine enantiomers which range covered 30–400 ng L−1. The method detection limits were between 0.65 and 11.5 ng L−1 and the method quantification limits were between 1.98 and 19.7 ng L−1. The identity of all enantiomers was confirmed using two MS/MS transitions and its ion ratios, according to European Commission Decision 2002/657/EC. This method was successfully applied to evaluate effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ≠ 0.5). The enantioselective validated method was able to monitor chiral pharmaceuticals in WWTP effluents and has potential to assess the enantioselective biodegradation in bioreactors. Further application in environmental matrices as surface and estuarine waters can be exploited.

Solid contact PVC membrane electrodes based on neutral or charged carriers for the selective reading of anionic sulfamethoxazole and their application to the analysis of aquaculture water

Sulfamethoxazole (SMX) is among the antibiotics employed in aquaculture for prophylactic and therapeutic reasons. Environmental and food spread may be prevented by controlling its levels in several stages of fish farming. The present work proposes for this purpose new SMX selective electrodes for the potentiometric determination of this sulphonamide in water. The selective membranes were made of polyvinyl chloride (PVC) with tetraphenylporphyrin manganese (III) chloride or cyclodextrin-based acting as ionophores. 2-nitrophenyl octyl ether was employed as plasticizer and tetraoctylammonium, dimethyldioctadecylammonium bromide or potassium tetrakis (4-chlorophenyl) borate was used as anionic or cationic additive. The best analytical performance was reported for ISEs of tetraphenylporphyrin manganese (III) chloride with 50% mol of potassium tetrakis (4-chlorophenyl) borate compared to ionophore. Nersntian behaviour was observed from 4.0 × 10−5 to 1.0 × 10−2 mol/L (10.0 to 2500 µg/mL), and the limit of detection was 1.2 × 10−5 mol/L (3.0 µg/mL). In general, the electrodes displayed steady potentials in the pH range of 6 to 9. Emf equilibrium was reached before 15 s in all concentration levels. The electrodes revealed good discriminating ability in environmental samples. The analytical application to contaminated waters showed recoveries from 96 to 106%.

Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 μg/L and 1 to 50 μg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) > 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, <15%) and accuracy (<20%), and stability. The limit of detection was 0.58 μg/L in urine and 1.47 μg/L in plasma for THPI and 1.14 and 2.17 μg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine.

Investigations into the extraction and the determination of polycyclic aromatic hydrocarbons (PAHs) from water by solid-phase extraction and capillary gas chromatography/ mass spectrometry

Factors affecting the detennination of PAHs by capillary GC/MS were studied. The effect of the initial column temperature and the injection solvent on the peak areas and heights of sixteen PAHs, considered as priority pollutants, USillg crosslinked methyl silicone (DB!) and 5% diphenyl, 94% dimethyl, 1% vinyl polysiloxane (DBS) columns was examined. The possibility of using high boiling point alcohols especially butanol, pentanol, cyclopentanol, and hexanol as injection solvents was investigated. Studies were carried out to optimize the initial column temperature for each of the alcohols. It was found that the optimum initial column temperature is dependent on the solvent employed. The peak areas and heights of the PAHs are enhanced when the initial column temperature is 10-20 c above the boiling point of the solvent using DB5 column, and the same or 10 C above the boiling point of the solvent using DB1 column. Comparing the peak signals of the PAHs using the alcohols, p-xylene, n-octane, and nonane as injection solvents, hexanol gave the greatest peak areas and heights of the PAHs particularly the late-eluted peaks. The detection limits were at low pg levels, ranging from 6.0 pg for fluorene t9 83.6 pg for benzo(a)pyrene. The effect of the initial column temperature on the peak shape and the separation efficiency of the PARs was also studied using DB1 and DB5 columns. Fronting or splitting of the peaks was obseIVed at very low initial column temperature. When high initial column temperature was used, tailing of the peaks appeared. Great difference between DB! and.DB5 columns in the range of the initial column temperature in which symmetrical.peaks of PAHs can be obtained is observed. Wider ranges were shown using DB5 column. Resolution of the closely-eluted PAHs was also affected by the initial column temperature depending on the stationary phase employed. In the case of DB5, only the earlyeluted PAHs were affected; whereas, with DB1, all PAHs were affected. An analytical procedure utilizing solid phase extraction with bonded phase silica (C8) cartridges combined with GC/MS was developed to analyze PAHs in water as an alternative method to those based on the extraction with organic solvent. This simple procedure involved passing a 50 ml of spiked water sample through C8 bonded phase silica cartridges at 10 ml/min, dried by passing a gentle flow of nitrogen at 20 ml/min for 30 sec, and eluting the trapped PAHs with 500 Jll of p-xylene at 0.3 ml/min. The recoveries of PAHs were greater than 80%, with less than 10% relative standard deviations of nine determinations. No major contaminants were present that could interfere with the recognition of PAHs. It was also found that these bonded phase silica cartridges can be re-used for the extraction of PAHs from water.

Polytypism and Silicon carbide : a solid state nuclear magnetic resonance study

A survey of predominantly industrial silicon carbide has been carried out using Magic Angle Spinning nuclear magnetic resonance (MAS nmr); a solid state technique. Three silicon carbide polytypes were studied; 3C, 6H, and 15R. The 13C and 29 Si MAS nmr spectra of the bulk SiC sample was identified on the basis of silicon (carbon) site type in the d iff ere n t pol Y t Y pes • Out to 5.00 A fro mac en t r a lsi 1 i con (0 r carbon) atom four types of sites were characterized using symmetry based calculations. This method of polytype analysis was also considered, in the prelminary stages, for applications with other polytypic material; CdBr 2 , CdI 2 , and PbI 2 " In an attempt to understand the minor components of silicon carbide, such as its surface, some samples were hydrofluoric acid washed and heated to extreme temperatures. Basically, an HF removable species which absorbs at -110 ppm (Si0 2 ) in the 29 Si MAS nmr spectrum is found in silicon carbide after heating. Other unidentified peaks observed at short recycle delays in some 29 Si MAS nmr spectra are considered to be impurities that may be within the lattice. These components comprise less than 5% of the observable silicon. A Tl study was carried out for 29 Si nuclei in a 3C ii polytype sample, using the Driven Equilibrium Single-Pulse Observation of T1 (DESPOT) technique. It appears as though there are a number of nuclei that have the same chemical shift but different T1 relaxation times. The T1 values range from 30 seconds to 11 minutes. Caution has to be kept when interpreting these results because this is the first time that DESPOT has been used for solid samples and it is not likely in full working order. MAS nmr indicates that the 13C and 29 Si ~sotropic chemical shifts of silicon carbide appear to have a reciprocal type of relationship_ Single crystal nmr analysis of a 6H sample is accordance with this finding when only the resultant isotropic shift is considered. However, single crystal nmr also shows that the actual response of the silicon and carbon nuclear environment to the applied magnetic field at various angles is not at all reciprocal. Such results show that much more single crystal nmr work is required to determine the actual behavior of the local magnetic environment of the SiC nuclei.

Electrospinning and characterization of self-assembled inclusion complexies

L’électrofilage est une technique permettant de fabriquer des fibres polymériques dont le diamètre varie entre quelques nanomètres et quelques microns. Ces fibres ont donc un rapport surface/volume très élevé. Les fibres électrofilées pourraient trouver des applications dans le relargage de médicaments et le génie tissulaire, comme membranes et capteurs chimiques, ou dans les nanocomposites et dispositifs électroniques. L’électrofilage était initialement utilisé pour préparer des toiles de fibres désordonnées, mais il est maintenant possible d’aligner les fibres par l’usage de collecteurs spéciaux. Cependant, il est important de contrôler non seulement l’alignement macroscopique des fibres mais aussi leur orientation au niveau moléculaire puisque l’orientation influence les propriétés mécaniques, optiques et électriques des polymères. Les complexes moléculaires apparaissent comme une cible de choix pour produire des nanofibres fortement orientées. Dans les complexes d’inclusion d’urée, les chaînes polymères sont empilées dans des canaux unidimensionnels construits à partir d’un réseau tridimensionnel de molécules d’urée liées par des ponts hydrogène. Ainsi, les chaînes polymère sonts très allongées à l’échelle moléculaire. Des nanofibres du complexe PEO-urée ont été préparées pour la première fois par électrofilage de suspensions et de solutions. Tel qu’attendu, une orientation moléculaire inhabituellement élevée a été observée dans ces fibres. De tels complexes orientés pourraient être utilisés à la fois dans des études fondamentales et dans la préparation de matériaux hiérarchiquement structurés. La méthode d’électrofilage peut parfois aussi être utilisée pour préparer des matériaux polymériques métastables qui ne peuvent pas être préparés par des méthodes conventionnelles. Ici, l’électrofilage a été utilisé pour préparer des fibres des complexes stables (α) et "métastables" (β) entre le PEO et l’urée. La caractérisation du complexe β, qui était mal connu, révèle un rapport PEO:urée de 12:8 appartenant au système orthorhombique avec a = 1.907 nm, b = 0.862 nm et c = 0.773 nm. Les chaînes de PEO sont orientées selon l’axe de la fibre. Leur conformation est significativement affectée par les ponts hydrogène. Une structure en couches a été suggérée pour la forme β, plutôt que la structure conventionnelle en canaux adoptée par la forme α. Nos résultats indiquent que le complexe β est thermodynamiquement stable avant sa fonte et peut se transformer en forme α et en PEO liquide par un processus de fonte et recristallisation à 89 ºC. Ceci va dans le sens contraire aux observations faites avec le complexe β obtenu par trempe du complexe α fondu. En effet, le complexe β ainsi obtenu est métastable et contient des cristaux d’urée. Il peut subir une transition de phases cinétique solide-solide pour produire du complexe α dans une vaste gamme de températures. Cette transition est induite par un changement de conformation du PEO et par la formation de ponts hydrogène intermoléculaires entre l’urée et le PEO. Le diagramme de phases du système PEO-urée a été tracé sur toute la gamme de compositions, ce qui a permis d’interpréter la formation de plusieurs mélanges qui ne sont pas à l’équilibre mais qui sont été observés expérimentalement. La structure et le diagramme de phases du complexe PEO-thiourée, qui est aussi un complexe très mal connu, ont été étudiés en détail. Un rapport molaire PEO :thiourée de 3:2 a été déduit pour le complexe, et une cellule monoclinique avec a = 0.915 nm, b = 1.888 nm, c = 0.825 nm et β = 92.35º a été déterminée. Comme pour le complexe PEO-urée de forme β, une structure en couches a été suggérée pour le complexe PEO-thiourée, dans laquelle les molécules de thiourée seraient disposées en rubans intercalés entre deux couches de PEO. Cette structure en couches pourrait expliquer la température de fusion beaucoup plus faible des complexes PEO-thiourée (110 ºC) et PEO-urée de forme β (89 ºC) en comparaison aux structures en canaux du complexe PEO-urée de forme α (143 ºC).

Luminescence from Surfactant-Free ZnO Quantum Dots Prepared by Laser Ablation in Liquid

Highly transparent, luminescent and biocompatible ZnO quantum dots were prepared in water, methanol, and ethanol using liquid-phase pulsed laser ablation technique without using any surfactant. Transmission electron microscopy analysis confirmed the formation of good crystalline ZnO quantum dots with a uniform size distribution of 7 nm. The emission wavelength could be varied by varying the native defect chemistry of ZnO quantum dots and the laser fluence. Highly luminescent nontoxic ZnO quantum dots have exciting application potential as florescent probes in biomedical applications.

Field Equilibrium Finite Elements for Structural Analysis

Many finite elements used in structural analysis possess deficiencies like shear locking, incompressibility locking, poor stress predictions within the element domain, violent stress oscillation, poor convergence etc. An approach that can probably overcome many of these problems would be to consider elements in which the assumed displacement functions satisfy the equations of stress field equilibrium. In this method, the finite element will not only have nodal equilibrium of forces, but also have inner stress field equilibrium. The displacement interpolation functions inside each individual element are truncated polynomial solutions of differential equations. Such elements are likely to give better solutions than the existing elements.In this thesis, a new family of finite elements in which the assumed displacement function satisfies the differential equations of stress field equilibrium is proposed. A general procedure for constructing the displacement functions and use of these functions in the generation of elemental stiffness matrices has been developed. The approach to develop field equilibrium elements is quite general and various elements to analyse different types of structures can be formulated from corresponding stress field equilibrium equations. Using this procedure, a nine node quadrilateral element SFCNQ for plane stress analysis, a sixteen node solid element SFCSS for three dimensional stress analysis and a four node quadrilateral element SFCFP for plate bending problems have been formulated.For implementing these elements, computer programs based on modular concepts have been developed. Numerical investigations on the performance of these elements have been carried out through standard test problems for validation purpose. Comparisons involving theoretical closed form solutions as well as results obtained with existing finite elements have also been made. It is found that the new elements perform well in all the situations considered. Solutions in all the cases converge correctly to the exact values. In many cases, convergence is faster when compared with other existing finite elements. The behaviour of field consistent elements would definitely generate a great deal of interest amongst the users of the finite elements.

Synthesis of dimethyl acetal of ketones: design of solid acid catalysts for one-pot acetalization reaction

The synthesis of dimethyl acetals of carbonyl compounds such as cyclohexanone, acetophenone, and benzophenone has successfully been carried out by the reaction between ketones and methanol using different solid acid catalysts. The strong influence of the textural properties of the catalysts such as acid amount and adsorption properties (surface area and pore volume) determine the catalytic activity. The molecular size of the reactants and products determine the acetalization ability of a particular ketone. The hydrophobicity of the various rare earth exchanged Mg–Y zeolites, K-10 montmorillonite clay, and cerium exchanged montmorillonite (which shows maximum activity) is more determinant than the number of active sites present on the catalyst. The optimum number of acidic sites as well as dehydrating ability of Ce3+-montmorillonite and K-10 montmorillonite clays and various rare earth exchanged Mg–Y zeolites seem to work well in shifting the equilibrium to the product side.

Solid Waste Management: A Case Study of Arppukara Grama Panchayat Of Kottayam District, Kerala (India)

The rising pressure of Population, together with the constantly changing technologies, and development perspectives, contribute to the ever increasing volumes of wastes in different forms. The solid and liquid wastes generated in the urban areas were considered a burden to the society, and hazardous to the environment. The fact is that the growth of consumerist culture and aimless throwing of refuse by the people created the outbreak of environmental pollution. Unhygienic environment and solid waste accumulation coincided with mosquito breeding which causes, the spread of most epidemics. The rationale behind most of the diseases is the unhygienic pattern followed by the people both in rural and urban areas. As an environmental package, the disposal of solid waste from different sources, such as house holds markets, commercial areas, slaughter houses, hospitals and industries, therefore assumed crucial importance. So as a part of the theory and practice, a study on the area, solid waste management of Arppukara Grama Panchayat of Kottayam district is taken into consideration. The study conducted here proposes, to examine the quality and quantity of the solid waste generated in the panchayat and also it's impact on the existing social, economical, environmental and ecological systems