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Controlling the Formation of Benzoic Acid: Isonicotinamide Molecular Complexes.Seaton, Colin C., Parkin, A., Wilson, C.C., Blagden, Nicholas 01 1900 (has links)
No / The formation of crystalline molecular complexes of benzoic acid and isonicotinamide with 1:1 and 2:1 compositions
has been investigated through solution cocrystallization. The 1:1 complex was solely obtained from ethanol solutions, while either
complex could be grown from aqueous and methanol solution by variation of the initial composition. The crystal structures of the
2:1 complex and a monohydrate of isonicotinamide were determined by single crystal X-ray diffraction. The intermolecular interactions
in the crystal structure of the complex were compared with other published carboxylic acid:isonicotinamide molecular complexes,
which highlights the robust nature of the acid · · · pyridine and acid · · · amide hydrogen bond, which exist in most cases. Complementary
computational studies into the binding of pairs of these molecules by ab initio calculations were found to support the experimental
observations and highlight the role of solvent in controlling the final crystalline form for multicomponent systems, through altering
the hierarchy of intermolecular interactions.
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Artificial neural networks modelling the prednisolone nanoprecipitation in microfluidic reactorsAli, Hany S.M., Blagden, Nicholas, York, Peter, Amani, Amir, Brook, Toni 2009 June 1928 (has links)
No / This study employs artificial neural networks (ANNs) to create a model to identify relationships between
variables affecting drug nanoprecipitation using microfluidic reactors. The input variables examined were
saturation levels of prednisolone, solvent and antisolvent flowrates, microreactor inlet angles and internal
diameters, while particle size was the single output. ANNs software was used to analyse a set of data
obtained by random selection of the variables. The developed model was then assessed using a separate
set of validation data and provided good agreement with the observed results. The antisolvent flow rate
was found to have the dominant role on determining final particle size.
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Preparation of hydrocortisone nanosuspension through a bottom-up nanoprecipitation technique using microfluidic reactors.Ali, Hany S.M., York, Peter, Blagden, Nicholas 22 June 2009 (has links)
No / In this work, the possibility of bottom-up creation of a relatively stable aqueous hydrocortisone nanosuspension
using microfluidic reactors was examined. The first part of the work involved a study of the
parameters of the microfluidic precipitation process that affect the size of generated drug particles.
These parameters included flow rates of drug solution and antisolvent, microfluidic channel diameters,
microreactors inlet angles and drug concentrations. The experimental results revealed that hydrocortisone
nano-sized dispersions in the range of 80¿450nm were obtained and the mean particle size could
be changed by modifying the experimental parameters and design of microreactors. The second part of
the work studied the possibility of preparing a hydrocortisone nanosuspension using microfluidic reactors.
The nano-sized particles generated from a microreactor were rapidly introduced into an aqueous
solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system
was then used to concentrate the prepared nanosuspension. The nanosuspension produced was then
characterized using photon correlation spectroscopy (PCS), Zeta potential measurement, transmission
electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray analysis. Results showed
that a narrowsized nanosuspension composed of amorphous spherical particles with a mean particle size
of 500±64 nm, a polydispersity index of 0.21±0.026 and a zeta potential of ¿18±2.84mVwas obtained.
Physical stability studies showed that the hydrocortisone nanosuspension remained homogeneous with
slight increase in mean particle size and polydispersity index over a 3-month period.
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Solubility of Budesonide, Hydrocortisone, and Prednisolone in Ethanol plus Water Mixtures at 298.2 KAli, Hany S.M., York, Peter, Blagden, Nicholas, Soltanpour, S., Acree, W.E. Jr., Jouyban, A. 01 1900 (has links)
No / Experimental solubilities of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2
K are reported. The solubility of drugs was increased with the addition of ethanol and reached the maximum
values of the volume fractions of 90 %, 80 %, and 80 % of ethanol. The Jouyban-Acree model was used to fit
the experimental data, and the solubilities were reproduced using previously trained versions of the Jouyban-Acree
model and the solubility data in monosolvents in which the overall mean relative deviations (OMRDs) of the
models were 5.1 %, 6.4 %, 37.7 %, and 35.9 %, respectively, for the fitted model, the trained version for ethanol
+ water mixtures, and generally trained versions for various organic solvents + water mixtures. Solubilities
were also predicted by a previously established log-linear model of Yalkowsky with the OMRD of 53.8 %.
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Three new hydrochlorothiazide cocrystals: Structural analyses and solubility studiesRanjan, S., Devarapalli, R., Kundu, S., Vangala, Venu R., Ghosh, A., Reddy, C.A. 09 December 2016 (has links)
Yes / Hydrochlorothiazide (HCT) is a diuretic BCS class IV drug with poor aqueous solubility and low permeability leading to poor oral absorption. The present work explores the cocrystallization technique to enhance the aqueous solubility of HCT. Three new cocrystals of HCT with water soluble coformers phenazine (PHEN), 4-dimethylaminopyridine (DMAP) and picolinamide (PICA) were prepared successfully by solution crystallization method and characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), fourier transform –infraredspectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Structural characterization revealed that the cocrystals with PHEN, DMAP and PICA exists in P21/n, P21/c and P21/n space groups, respectively. The improved solubility of HCT-DMAP (4 fold) and HCT-PHEN (1.4 fold) cocrystals whereas decreased solubility of HCT-PICA (0.5 fold) as compared to the free drug were determined after 4 h in phosphate buffer, pH 7.4, at 25 °C by using shaking flask method. HCT-DMAP showed a significant increase in solubility than all previously reported cocrystals of HCT suggest the role of a coformer. The study demonstrates that the selection of coformer could have pronounced impact on the physicochemical properties of HCT and cocrystallization can be a promising approach to improve aqueous solubility of drugs.
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Structural similarity in chiral-achiral multi-component crystalsScowen, I.J., Alomar, T.S., Munshi, T., Seaton, Colin C. 15 April 2020 (has links)
Yes / The creation of multi-component crystals between chiral and achiral components has gained increased interest in recent years. In many cases the overall crystal structure is similar with the creation of a pseudo-inversion centre in the enantiopure case. This allows for the formation of solid solutions between the two extremes, which may have applications within chiral resolution. Utilising a combination of database mining, computational prediction and experimental screening, the frequency of formation for such materials has been investigated showing that for co-crystals this occurs more frequently than for salts, though there is a limited number of samples to draw structural conclusions. Computational modelling indicates the prediction of such systems can be challenging due to the similarities in energy of many crystal structures, so development of tools to design such systems is required to fully utilise these concepts. / The Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program.
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Construction of Ternary Phase Diagrams: Application of Quantitative NMRTelford, Richard, Obule, Whitney, Seaton, Colin C. 01 May 2022 (has links)
Yes / The growth of cocrystalline phases continues to expand as a key area of crystal engineering research. Understanding the phase behavior of the material and controlling the crystalline form of the material from a solution-based route can be aided by the construction of a ternary phase diagram for the system. A range of methods exist for this process which display a variety of costs and time to achieve the final diagram. The application of quantitative NMR (qNMR) to this problem offers a fast analysis method to directly determine the solution composition of all species (coformers and solvent) and is demonstrated to successfully allow the construction of ternary diagrams with and without a cocrystal phase being formed for systems with high and low solubility.
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Linear und tetragonal strukturierte Tektone mit peripheren Aminosäure- und PeptidhaftgruppenEißmann, Frank 10 October 2011 (has links) (PDF)
Im Rahmen der vorliegenden Arbeit gelang die Synthese einer Reihe von neuartigen linear oder tetragonal präorganisierten tektonischen Verbindungen mit peripheren Haftgruppen, bestehend aus den natürlich vorkommenden Aminosäuren Glycin und L-Alanin oder kurzen Peptiden. Neben der Synthese stand die strukturelle Charakterisierung der Zielsubstanzen und Vorstufen im Vordergrund, wobei die Aufklärung der Kristallstrukturen einer Zielverbindung und elf relevanter Vorstufen gelang, deren Packungsstrukturen überwiegend durch N–H•••O-Interaktionen determiniert sind. Ergänzend konnten Informationen bezüglich der von den Haftgruppen gebildeten Strukturmotive im Festkörper mittels FT-IR-Spektroskopie abgeleitet werden. Die Auswertung konformationssensitiver 1H- und 13C-NMR-Signale zeigt, dass Aminosäurereste innerhalb identischer Haftgruppen in Lösung jeweils in derselben Konformation vorliegen. Fluoreszenzspektroskopische Untersuchungen der hergestellten Zielverbindungen lassen interessante Anwendungen auf dem Gebiet der Sensorik erwarten.
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Linear und tetragonal strukturierte Tektone mit peripheren Aminosäure- und PeptidhaftgruppenEißmann, Frank 02 September 2011 (has links)
Im Rahmen der vorliegenden Arbeit gelang die Synthese einer Reihe von neuartigen linear oder tetragonal präorganisierten tektonischen Verbindungen mit peripheren Haftgruppen, bestehend aus den natürlich vorkommenden Aminosäuren Glycin und L-Alanin oder kurzen Peptiden. Neben der Synthese stand die strukturelle Charakterisierung der Zielsubstanzen und Vorstufen im Vordergrund, wobei die Aufklärung der Kristallstrukturen einer Zielverbindung und elf relevanter Vorstufen gelang, deren Packungsstrukturen überwiegend durch N–H•••O-Interaktionen determiniert sind. Ergänzend konnten Informationen bezüglich der von den Haftgruppen gebildeten Strukturmotive im Festkörper mittels FT-IR-Spektroskopie abgeleitet werden. Die Auswertung konformationssensitiver 1H- und 13C-NMR-Signale zeigt, dass Aminosäurereste innerhalb identischer Haftgruppen in Lösung jeweils in derselben Konformation vorliegen. Fluoreszenzspektroskopische Untersuchungen der hergestellten Zielverbindungen lassen interessante Anwendungen auf dem Gebiet der Sensorik erwarten.
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Hydrogen-bond driven supramolecular chemistry for modulating physical properties of pharmaceutical compoundsForbes, Safiyyah January 1900 (has links)
Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / The ability to predict and control molecular arrangements without compromising the individual molecules themselves still remains an important goal in supramolecular chemistry. This can be accomplished by establishing a hierarchy of intermolecular interactions such as hydrogen and halogen bond, which may facilitate supramolecular assembly processes.
Several acetaminopyridine/acetaminomethylpyridine supramolecular reactants (SR’s) were prepared with aliphatic carboxylic acids in order to determine patterns of molecular recognition preferences of the N-H moiety. The results obtained revealed the formation of molecular cocrystals through heteromeric O-H…N/N-H…O hydrogen bonds with the acetaminopyridine/acetaminomethylpyridine binding site. Furthermore, the SR’s also reacted with metal ions resulting in robust 1D and 2D metal-containing architectures.
A series of pyridyl/pyrazine mono-N-oxide compounds were synthesized and reacted with a variety of halogenated benzoic acids, in order to assess the ability of these molecules to establish binding selectivity when both a hydrogen and halogen bond donor is present. The results obtained revealed that the pyridyl/carboxylic acid synthon formed 7/7 times and halogen bonds (N-O…I or N-O…Br) extended the SR/acid dimers into 1D and 2D networks. These results were rationalized via charge calculations as well as through the hierarchical view of intermolecular interactions consisting of hydrogen and halogen bonds.
Furthermore, a series of thienyl compounds were synthesized and allowed to react with halogen bond donors to determine whether the halogen bond is purely electrostatic or based on the hard and soft acids and bases principles. The results obtained showed that of the 34 reactions between a halogen bond donor and thienyl compounds, the halogen bond is predominantly electrostatic in nature.
Finally, as a result of our improved understanding on molecular recognition, we were able to carry out systematic structure-property studies on a series of cocrystals of anti-cancer drug molecules with aliphatic carboxylic acids. This study revealed that systematic changes to the molecular nature of the co-crystallizing agent combined with control over the way individual building blocks are organized within the crystalline lattice makes it possible to establish predictable links between molecular structure and macroscopic physical properties, such as melting behavior, solubility, dissolution rate, etc.
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