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Paracetamol trihydrate is a highly unstable form which undergoes a rapid phase transformation to its stable anhydrous polymorph I. In situ Raman surface mapping on a trihydrate sample provides evidence for the existence of a transient phase on the route to its stable polymorph I. The transient phase showed significant spectral differences from those of known polymorphs, the trihydrate and amorphous forms, and is tentatively assigned to the monohydrate form on the basis of the observed crystallite morphology. [ABSTRACT FROM AUTHOR]

We report the first systematic characterisation of data sub-selection with multivariate analysis to be applied to either TRS or the low-wavenumber Raman region. A model pharmaceutical formulation comprising two polymorphs mixed in the range of 1–99% is investigated. For data sub-selection, sparse partial least squares is for the first time applied to TRS data and compared with principal component analysis. It is found that low-wavenumber data (50–340 cm−1) are demonstrably superior for quantitative modelling than data in the more conventional mid-wavenumber range (340–2000 cm−1). Our results point the way to enhanced quantitative analytical capabilities for TRS, with potential application areas including pharmaceuticals, security and process-analytical technology, by combining data sub-selection with low-wavenumber-capable optics. [ABSTRACT FROM AUTHOR]

We present the first quantitative study of polymorphic content in a model pharmaceutical formulation using transmission Raman spectroscopy (TRS), and compare the results obtained with those from traditional backscattering geometry. The transmission method is shown to provide a true bulk measurement of the composition, being unaffected by systematic or stochastic sub-sampling issues that can plague traditional backscattering geometries. The accuracy of the quantification of the polymorphs using TRS was shown to surpass considerably that achieved using conventional backscattering mode. For a model-free fit, the TRS method yielded R2of 0.996 compared to the backscattering value of 0.802; for a partial least squares fit with a single component the TRS method accounted for 98.09% of the variance in the data and yielded an R2of 0.985, compared to 89.65% of the variance and R2of 0.804 for the backscattering method. [ABSTRACT FROM AUTHOR]

The formation of the layered double hydroxide [Cu2Cr(OH)6]Cl·yH2O from the reaction between CuO and aqueous CrCl3·6H2O was explored using synchrotron X-ray diffraction and ex situ analyses. The use of hard X-rays permitted time-resolved in situ studies to be performed as the reaction proceeded under a range of conditions. Additional information was obtained from ex situ experiments in which aliquots of the reaction mixture were removed, quenched, and subsequently analysed by laboratory X-ray diffraction, IR, UV-visible, and atomic emission spectroscopies. On the basis of these data, it is proposed that the reaction involves three steps. First, the solid CuO starting material is hydrolysed to give Cu(OH)2 chains, releasing Cu(2+) ions into solution. The Cu hydroxide chains subsequently condense with aqueous Cr(3+) species, Cl(-) ions and water molecules to give a hydrated form of the LDH. This material then extrudes some water to form a phase with a reduced interlayer spacing.

Polymer microarrays are a key enabling technology for the discovery of novel materials. This technology can be further enhanced by expanding the combinatorial space represented on an array. However, not all materials are compatible with the microarray format and materials must be screened to assess their suitability with the microarray manufacturing methodology prior to their inclusion in a materials discovery investigation. In this study a library of materials expressed on the microarray format are assessed by light microscopy, atomic force microscopy and time-of-flight secondary ion mass spectrometry to identify compositions with defects that cause a polymer spot to exhibit surface properties significantly different from a smooth, round, chemically homogeneous 'normal' spot. It was demonstrated that the presence of these defects could be predicted in 85% of cases using a partial least square regression model based upon molecular descriptors of the monomer components of the polymeric materials. This may allow for potentially defective materials to be identified prior to their formation. Analysis of the PLS regression model highlighted some chemical properties that influenced the formation of defects, and in particular suggested that mixing a methacrylate and an acrylate monomer and/or mixing monomers with long and linear or short and bulky pendant groups will prevent the formation of defects. These results are of interest for the formation of polymer microarrays and may also inform the formulation of printed polymer materials generally.

Transmission Raman spectroscopy is employed for the first time to analyse model formulations comprising tabletted cocrystals. The ability of transmission Raman to differentiate between formulations on the basis of both drug loading and drug chemistry (cocrystal versus separate components) is investigated.

Comparison of structure and hydration stability of pairs of chiral and racemic binary cocrystals indicates that the racemic solid is more stable than the chiral one; we illustrate that this difference might arise from intermolecular (crystal packing) factors in one case, while intramolecular (molecular conformation) factors are more significant in the other.

The reaction between pairs of enantiomeric cocrystals involving caffeine or theophylline and a chiral cocrystal former has been investigated by liquid-assisted grinding: we demonstrate two different outcomes for such cocrystal-cocrystal reactions.

Manganocene, Cp(2)Mn, has been employed as a precursor in the synthesis of a range of Mn(II) dimers of the type [CpMn(micro-X)](2)[X = 8-NHC(9)H(6)N (1), N(Ph)(C(5)H(4)N)(2), N(4-EtC(6)H(4))(C(5)H(4)N)(3) and C[triple bond]CPh (4)] as well as the bis-adduct [Cp(2)Mn[HN=C(NMe(2))(2)](2)](5). The solid-state structures of 1-5 are reported. Variable-temperature magnetic measurements have been used to assess the extent of Mn(micro-X)Mn communication within the dimers of 1-4 as a function of the bridging ligands (X).