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Carbon NMR chemical shit tensors are measured for two forms of solid 10-deacetyl baccatin lll to find out more about the origins of solid-state NMR shift differences in polymorphs. Tensor differences that were observed seem to be basically because of conformational variations in ring substituents and the cyclohexenyl ring.

Research was conducted to examine the application of the PHORMAT and FIREMAT solid-state NMR analyses to the terpene parthenolide to obtain all shift tensors. A comparison of the two sets of principal values can be carried out statistically to estimate the precision in the tensor measurements after having determined the tensors from both approaches. The assignments were given for all carbons and it was observed for the first time that most of the carbons may be assigned to one or the other of the two distinct molecules in the crystallographic asymmetric unit.

A study using single-crystal X-ray diffraction and solid-state 15N NMR spectroscopy examined an azobenzene dyestuff which goes through conformational exchange in the solid state. The combined utilization of the two techniques provided a thorough understanding of the disordered character of a common azobenzene dyestuff. The X-ray analysis demonstrated two conformations with an almost equal weighting within the asymmetric unit. Meanwhile, solid-state NMR showed that a motional process that interconverted two trans conformations on a time scale influenced the quality of the disorder.

McGeorge is an experienced analytical scientist with more than 13 years of industrial experience. He has led various projects in the area of PAT, noninvasive method development, materials characterization, and [...]

Hyperspectral chemical imaging technologies are frequently applied in the pharmaceutical industry to assess the distribution of ingredients in product intermediates and finished products. This article discusses two recognized measures of spatial uniformity in the context of pharmaceuticals. Synthetic images are used to introduce the utility of Ripley's K-function and the Herfindahl-Hirschman index (HHI) for describing image content. These metrics were applied to a commercial-like product to demonstrate the practical interpretation for product development. The simple approaches presented here offer the possibility of reporting objective measures of intra-tablet compositional uniformity with minimal supervision. [ABSTRACT FROM AUTHOR]

Two different crystalline polymorphs of valinomycin, the triclinic and monoclinic forms, have been studied by high resolution, solid state 13C CP-MAS NMR spectroscopy. Although the two polymorphs of the crystal are remarkably similar, there are distinct differences in the isotropic chemical shifts between the two spectra. For the triclinic form, the carbon chemical shift tensor components for the alpha carbons adjacent to oxygen in the lactic acid and hydroxyisovaleric acid residues and the ester carbonyls of the valine residue were obtained using the FIREMAT experiment. From the measured components, it was found that the behavior of the isotropic chemical shift, δiso, for valine residue ester carbonyl carbons is predominately influenced by the intermediate component, δ22. Additionally it was found that the smallest shift component, δ33, for the L-lactic acid (L-Lac) and D-α-hydroxyisovaleric acid (D-Hyi) Cα -O carbon was significantly displaced depending upon the nature of individual amino acid residues, and it is the δ33 component that governs the behavior of δiso in these alpha carbons. [ABSTRACT FROM AUTHOR]

A sensitive, high-resolution 'FIREMAT' two-dimensional (2D) magic-angle-turning experiment is described that measures chemical shift tensor principal values in powdered solids. The spectra display spinning-sideband patterns separated by their isotropic shifts. The new method's sensitivity and high resolution in the isotropic-shift dimension result from combining the 5pi magic-angle-turning pulse sequence, an extension of the pseudo-2D sideband-suppression data rearrangement, and the TIGER protocol for processing 2D data. TPPM decoupling is used to enhance resolution. The method requires precise synchronization of the pulses and sampling to the rotor position. It is shown that the technique obtains 35 natural-abundance 13C tensors from erythromycin in 19 hours, and high quality naturalabundance 15N tensors from eight sites in potassium penicillin V in three days on a 400MHz spectrometer. [ABSTRACT FROM AUTHOR]

Presents a study which described the application of PHORMAT and FIREMAT solid-state nuclear magnetic resonance (NMR) techniques in analyzing shift values in terpene parthenolide. Explanation of the NMR analysis techniques; Methodology used; Results and discussion; Conclusion.

Abstract: In a Quality by Design (QbD) development environment the effect of early process parameters on downstream manufacturing parameters, and the ultimate effect on drug product quality, need to be understood. For poorly soluble drugs, size reduction is frequently employed to obtain consistent in-vivo exposures. As a result, micronization is a key early stage processing step for many active pharmaceutical ingredients (APIs). This paper demonstrates the effect of varying micronization conditions on an API for which micronization is deemed necessary to ensure consistent drug delivery after human administration. Material micronized to different extents are confirmed as different by surface area, surface energy, particle size analysis, bulk density and surface adhesion measurements. These material characteristics can be correlated with the outcomes from a key processing step, blending. The evolution of the blending process is followed using PAT techniques, so that an overall understanding of the relationship between particle properties and blend uniformity can be demonstrated. Execution of such a study during drug development can enable selection of the appropriate control strategy to ensure production of API in the desired range where consistent optimal bioavailability and downstream processability are achieved. [Copyright &y& Elsevier]

Transmission near-infrared (NIR) measurements of a 1 mm thick aspirin disk were made at different positions as it was moved through a stack of eight 0.5 mm thick disks of microcrystalline cellulose (Avicel). The magnitude of the first derivative of absorbance for the aspirin interlayer at 8934 cm−1was lower when the disk was placed at the top or bottom of the stack of Avicel disks, with the largest signal observed when the aspirin was positioned at the central positions. The variation in signal with depth is consistent with that observed previously for transmission Raman spectrometry. In both cases, the trend observed can be attributed to lower photon density at the air-sample interface, relative to the center of the sample, owing to loss of photons to the air. This results in a reduction in the number of photons absorbed or Raman photons generated and subsequently detected when the interlayer occupies a near-surface position. [ABSTRACT FROM AUTHOR]

We report the case of BMS-488043-PVP solid dispersions which when analysed using modulated DSC showed compliance with the Gordon–Taylor model, confirming ideal mixing behaviour of the two components. The nature or presence of stabilising interactions between drug and PVP could not be confirmed using this technique. Use of FT-IR, Raman and solid-state NMR spectroscopy confirmed the presence of stabilising hydrogen bond interactions between the drug and PVP. Similar interactions are present as intermolecular bonds in the crystalline and pure amorphous drug system. The Gordon–Taylor equation, as it is not predictive of the presence of intermolecular bonds such as hydrogen bonding in an amorphous dispersion, may underestimate the likely physical stability of solid dispersions which are produced and stabilised by these interactions. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3456–3468, 2009 [ABSTRACT FROM AUTHOR]

Reports on the measurement of carbon nuclear magnetic resonance (NMR) chemical shift tensors for two forms of solid 10-deacetyl baccatin III to investigate the origins of solid-state NMR. Finding that lattice interactions cannot fully account for the shift differences in the two forms; Possible appearance of the observed tensor differences from conformational variations in ring substituents.

To investigate the origins of solid-state NMR shift differences in polymorphs, carbon NMR chemical shift tensors are measured for two forms of solid 10-deacetyl baccatin III: a dimethyl sulfoxide (DMSO) solvate and an unsolvated form. A comparison of ab initio computed tensors that includes and omits the DMSO molecules demonstrates that lattice interactions cannot fully account for the shift differences in the two forms. Instead, conformational differences in the cyclohexenyl, benzoyl, and acetyl moieties are postulated to create the differences observed. X-ray analysis of six baccatin III analogues supports the suggested changes in the cyclohexenyl and benzoyl systems. The close statistical match of the (13)C chemical shifts of both polymorphic forms with those calculated using the X-ray geometry of 10-deacetyl baccatin III supports the contention that the B, C, and D rings are fairly rigid. Therefore, the observed tensor differences appear to arise primarily from conformational variations in ring substituents and the cyclohexenyl ring.