Applications of ℓ\u3csub\u3e1\u3c/sub\u3e and Mixed H\u3csub\u3e2\u3c/sub\u3e/ℓ\u3csub\u3e1\u3c/sub\u3e Optimization

This thesis explores the use of ℓ1 and mixed H2/ℓ1 optimization methods to design flight control systems. ℓ1 optimization is used to handle tracking issues in the design of digital compensators. Control deflection and rate limitations, overshoot and undershoot limitations and steady-state error requirements are discussed. Model-matching techniques which produce acceptable tracking results with lower order controllers are also examined. New numerical methods for continuous H2/L1 and discrete H2/ℓ1 optimization are presented. These methods are used to design an aircraft controller in continuous and discrete time and the results are compared

Co-crystal structures of furosemide:urea and carbamazepine:indomethacin determined from powder x-ray diffraction data

Co-crystallization is a promising approach to improving both the solubility and the dissolution rate of active pharmaceutical ingredients. Crystal structure determination from powder diffraction data plays an important role in determining co-crystal structures, especially those generated by mechanochemical means. Here, two new structures of pharmaceutical interest are reported: a 1:1 co‑crystal of furosemide with urea formed by liquid-assisted grinding and a second polymorphic form of a 1:1 co‑crystal of carbamazepine with indomethacin, formed by solvent evaporation. Energy minimization using dispersion-corrected density functional theory was used in finalizing both structures. In the case of carbamazepine:indomethacin, this energy minimization step was essential in obtaining a satisfactory final Rietveld refinement

A carbamazepine-indomethacin (1:1) cocrystal produced by milling

An X-ray amorphous mixture of carbamazepine and indomethacin transforms upon annealing to produce a novel 1:1 cocrystal, whose structure has been determined from laboratory powder X-ray diffraction (PXRD) data

CDASH: a cloud-enabled program for structure solution from powder diffraction data

The simulated annealing approach to crystal structure determination from powder diffraction data, as implemented in the DASH program, is readily amenable to parallelization at the individual run level. Very large scale increases in speed of execution can be achieved by distributing individual DASH runs over a network of computers. The CDASH program delivers this by using scalable on-demand computing clusters built on the Amazon Elastic Compute Cloud service. By way of example, a 360 vCPU cluster returned the crystal structure of racemic ornidazole (Z0 = 3, 30 degrees of freedom) ca 40 times faster than a typical modern quad-core desktop CPU. Whilst used here specifically for DASH, this approach is of general applicability to other packages that are amenable to coarse-grained parallelism strategies

The principles underlying the use of powder diffraction data in solving pharmaceutical crystal structures

Solving pharmaceutical crystal structures from powder diffraction data is discussed in terms of the methodologies that have been applied and the complexity of the structures that have been solved. The principles underlying these methodologies are summarized and representative examples of polymorph, solvate, salt and cocrystal structure solutions are provided, together with examples of some particularly challenging structure determinations

Application of hydrogen-bond propensity calculations to an indomethacin–nicotinamide (1:1) co-crystal

The crystal structure of an indomethacin–nicotinamide (1 : 1) cocrystal produced by milling has been determined from laboratory powder X-ray diffraction (PXRD) data. The hydrogen bonding motifs observed in the structure represent one of the most probable of all the possible combinations of donors and acceptors in the constituent molecules

Encouraging independent thought and learning in first year practical classes

The transition from A-level to degree-level practical classes then to a research project, hence from dependent learner to independent researcher, is a hurdle that all students face when studying for a chemistry degree. This can be daunting so any innovations that aid this transition are of great value. At the University of Reading, the first year practical course has been redesigned to facilitate this transition by embedding independent thought and experimentation across all chemistry disciplines (introductory, organic, inorganic and physical). Examples of experiments that provide opportunities for independent student investigation, along with student perceptions of the experiments of the course, are given. Using this model for practical-class delivery, student engagement, confidence, independence and ultimately preparedness for year 2 were improved

Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media

The products of reactions of the pharmaceutical amide carbamazepine (CBZ) with strong acids under aqueous conditions were investigated by both powder and single crystal X-ray diffraction. Despite previous claims to the contrary, it was found that salt forms with CBZ protonated at the amide O atom could be isolated from reactions with both HCl and HBr. These forms include the newly identified hydrate phase [CBZ(H)][Cl]·H O. Reactions with other mineral acids (HI and HBF ) gave ionic cocrystalline (ICC) forms (CBZ· [acridinium][I ]·2.5I and CBZ·[H O ] [BF ] ·H O) as well as the salt form CBZ·[CBZ(H)][BF ]·0.5H O. Reaction 2 4 3 2 5 2 0.25 4 0.25 2 4 2 of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O SC H ], [CBZ(H)][O SC H (OH)]· 3 6 5 3 6 4 0.5H O, [CBZ(H)] [O SCH CH SO ], and [CBZ(H)][O SC H (OH) (COOH)]·H O. CBZ and protonated CBZ(H) 2 2 3 2 2 3 3 6 3 2 moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preference

Rietveld-based quantitative phase analysis of sugars in confectionery

Sugars are a near-ubiquitous ingredient in food products, yet rising rates of obesity and related illnesses have prompted a drive to reduce their content. The use of amorphous sugars in confectionery may be one way of achieving this by providing a similarly sweet sensation due to increased dissolution rate. However, accurate amorphous and crystalline form characterisation and quantification of complex foodstuffs can be difficult. In this study, a method for the quantification of crystalline and amorphous sugars in chocolate precursors, using powder X ray powder diffraction, is presented. The method was first validated by the use of known compositions of mixtures of amorphous and crystalline sugars, then employed in assessing two chocolate crumb samples. The results show that the method can reliably determine the absolute quantity of amorphous and crystalline components in a confectionery sample, whilst maintaining sample integrity, apart from the addition of an inert internal standard. As such, it is a valuable addition to other techniques currently used