You cannot fight the pressure: Structural rearrangements of active pharmaceutical ingredients under magic angle spinning

Although solid-state nuclear magnetic resonance (NMR) is a versatile analytical tool to study polymorphs and phase transitions of pharmaceutical molecules and products, this work summarizes examples of spontaneous and unexpected (and unwanted) structural rearrangements and phase transitions (amorphous-to-crystalline and crystalline-to-crystalline) under magic angle spinning (MAS) conditions, some of them clearly being due to the pressure experienced by the samples. It is widely known that such changes can often be detected by X-ray powder diffraction (XRPD); here, the capability of solid-state NMR experiments with a special focus on ¹H-¹³C frequency-switched Lee–Goldburg heteronuclear correlation (FSLG HETCOR)/MAS NMR experiments to detect even subtle changes on a molecular level not observable by conventional 1D NMR experiments or XRPD is presented. Furthermore, it is shown that a polymorphic impurity combined with MAS can induce a crystalline-to-crystalline phase transition. This showcases that solid-state NMR is not always noninvasive and such changes upon MAS should be considered in particular when compounds are studied over longer time spans.     

Growth, optical properties and laser performance of NdxLu1−xVO4 series crystals

Nd_xLu_1−xVO₄ (x = 0, 0.005, 0.02, 0.023, 0.03 and 0.05) series crystals have been grown by the Czochralski method. The results of X-ray powder diffraction experiments show that these crystals belong to the zircon-type structure. The cutoff wavelength of LuVO₄ is 330 nm and the transmittance is about 80% in 540-3010 nm. The functional relation of absorption coefficient α at 808 nm on Nd³⁺-doped concentration N_d in units of atomic % is obtained to be α = 7.649 N_d. The results of Judd-Ofelt analysis show that there is no obvious concentration quenching effect below 3 at.% doped concentrations. The highest output power at 1.06 μm is 1090 mW for Nd_0.02Lu_0.98VO₄ at the pumping power of 6.58 W of a laser diode, the optical-optical conversion efficiency is 16.6% and slope efficiency is 19.4%.     

Comprehensive Characterisation of the Ketoprofen-β-Cyclodextrin Inclusion Complex Using X-ray Techniques and NMR Spectroscopy

Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M⁻¹, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.     

Identification and spectra–structure determination of soil minerals: Raman study supported by IR spectroscopy and X‐ray powder diffraction

Raman and IR spectroscopy were used for the characterization of several minerals in morphologically similar vertisol sequences from Kiževak (Serbia). It helped us to establish the surface layer transition going from calcic vertisols (containing gypsum and calcite) to calcimagnesic vertisols (containing aragonite, magnesium‐calcite and dolomite) derived from peridotite and serpentinite. The observed band positions are found to be solely characteristic for each carbonate mineral and are used to discuss the main structural features of carbonates and sulfates present in the studied soil. It was found that the dolomite, calcite and aragonite concretions are present in the deepest layer of the soil, whereas the gypsum is found in the topsoil. The identification was confirmed of the carbonates having calcite and aragonite structure, and the representative from the sulfate group (gypsum) was confirmed by X‐ray powder diffraction. Copyright © 2009 John Wiley & Sons, Ltd.     

On the self-condensation of aminoguanidine leading to 1,1,4,10,10-pentaamino-2,3,5,6,8,9-hexaazadeca-1,3,5,7,9-pentaene (structure elucidation through X-ray powder diffraction)

Chemical and spectroscopic (UV; ¹H, ¹³C, ¹⁵N NMR; HRMS) studies determined the structure of 1,1,4,10,10-pentaamino-2,3,5,6,8,9-hexaazadeca-1,3,5,7,9-pentaene for the red-violet compound, which was obtained by treating aminoguanidine hydrochloride with KOH. X-ray powder diffraction and lattice-constrained PBC-DFT optimization confirmed this structure and defined a linear all-trans configuration.     

A comparison of glycans and polyglycans using solid-state NMR and X-ray powder diffraction

Individual polyglycans and their corresponding monomers have been studied separately for several decades. Attention has focused primarily on the modifications of these polyglycans instead of the simple relationship between the polyglycans themselves and their corresponding monomers. Two polyglycans, chitin and chitosan, were examined along with their respective monomeric units, N-acetyl-D-glucosamine (GlcNAc) and (+)D-glucosamine (GlcN) using solid-state proton decoupling Magic Angle Turning (MAT) techniques and X-Ray Powder Diffraction (XRPD). A down-field shift in isotropic (13)C chemical shifts was observed for both polymers in Cross Polarization/Magic Angle Spinning (CP/MAS) spectra. An explanation of misleading peak assignments in previous NMR studies for these polyglycans was determined by comparing sideband patterns of the polymers with their corresponding monomers generated in a 2D FIve pi REplicated Magic Angle Turning (FIREMAT) experiment processed by Technique for Importing Greater Evolution Resolution (TIGER). Structural changes in the crystalline framework were supported by XRPD diffraction data.     

Drug-excipient compatibility studies by physico-chemical techniques; The case of Indomethacin

This work exemplifies a general method of studying the drug excipient interactions, with the aim of predicting rapidly and inexpensively the long term stability of their mixtures. We study the physico-chemical properties of a drug (indomethacin) in the solid state and in different combinations with several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel^©). We compare the properties of pure compounds (untreated, or moisture/temperature conditioned) with those of binary mixtures drug:excipient which underwent the same treatment. The purpose is to find indications of interactions within the mixtures, which means a potential incompatibility of the excipient. Both morphological and thermal properties are sensitive to interactions which leave mostly unmodified the IR spectra and the X-rays patterns. In particular, we find that indomethacin does interact with PVP and MGST, but is certainly compatible with Avicel^©.     

Drug-excipient compatibility studies by physico-chemical techniques; The case of Atenolol

We apply a range of techniques (thermal methods, microscopy, X-ray diffraction, IR spectroscopy) to characterize a drug (atenolol), several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©) and drug-excipients mixtures either as prepared, annealed, and exposed to moisture. We compare the data of the mixtures with those computed from a weighted average of similarly treated pure compounds to find evidence of drug properties modified by the interaction with the excipient. We find that thermal response is by far the most sensitive indicator of interaction while IR is the least sensitive one. Avicel© has essentially no interaction with atenolol, while MGST modifies significantly only the thermal response of the drug in the MGST-rich mixtures. PVP interacts strongly with atenolol, and this interaction appears to be mediated by the substantial amount of hydration water the excipient brings in its mixtures with a water-free drug.     

The influence of storage conditions on the polymorphic stability of zolpidem tartrate hydrate

The polymorphic stability of a drug substance is a very important topic in the pharmaceutical industry. Differential scanning calorimetry, thermogravimetric analysis with the support of X-ray powder diffraction and infrared spectroscopy were used as screening techniques for testing structural changes of zolpidem tartrate hydrate stored under different conditions. Obtained data suggested that first structural changes occurred at the temperature of 25°C after 2 months of storage. DSC analysis showed that there was a two-step process of water elimination and lack of a phase transition in the temperature range from 130 to 170°C in comparison with an initial sample.     

Computational approach on architecture and tailoring of organic metal complexes derived from streptomycin and Zn,Cd and Pb: antimicrobial effectiveness

Streptomycin has been used to derive organic metal complexes (OMCs) after metallation with ZnCl₂, CdCl₂ and PbCl₂ and characterized by elemental analysis, electronic and vibrational spectroscopy, ¹H and ¹³C NMR, mass spectroscopy (time‐of‐flight MS), magnetic measurement, thermal decomposition analysis (TGA, DTA), molecular modeling and X‐ray powder diffraction. OMCs are monomeric. Crystal system, lattice parameters, unit cell, particle size and volume of crystalline OMCs have been determined using X‐ray powder diffraction pattern analysis. The geometries of complexes were optimized on the basis of molecular modeling. Kinetic parameters were computed from thermal analysis, confirming first‐order kinetics. Molecular models have been optimized by MM2 calculations. Architecture and tailoring of the rationally designed and synthesized supramolecular models having covalent bonded oxygen or other molecular contacts extended through Huckel Charge Distribution in highest occupied molecular orbit (HOMO). Antimicrobial effectiveness of OMCs has been reported. Copyright © 2011 John Wiley & Sons, Ltd.