Local Structural Effects Due to Micronization and Amorphization on an HIV Treatment Active Pharmaceutical Ingredient.

Processing procedures for inducing domain size reduction and/or amorphous phase generation can be crucial for enhancing the bioavailability of active pharmaceutical ingredients (APIs). It is important to quantify these reduced coherence phases and to detect and characterize associated structural changes, to ensure that no deleterious effects on safety, function, or stability occur. Here, X-ray powder diffraction (XRPD), total scattering pair distribution function (TSPDF) analysis, and solid-state nuclear magnetic resonance spectroscopy (SSNMR) have been performed on samples of GSK2838232B, an investigational drug for the treatment of human immunodeficiency virus (HIV).

Investigating gabapentin polymorphism using solid-state NMR spectroscopy.

Solid-state NMR spectroscopy (SSNMR), coupled with powder X-ray diffraction (PXRD), was used to identify the physical forms of gabapentin in samples prepared by recrystallization, spray drying, dehydration, and milling. Four different crystalline forms of gabapentin were observed: form I, a monohydrate, form II, the most stable at ambient conditions, form III, produced by either recrystallization or milling, and an isomorphous desolvate produced from desolvating the monohydrate. As-received gabapentin (form II) was ball-milled for 45 min in both the presence and absence of hydroxypropylcellulose (HPC).

The stabilizing effect of moisture on the solid-state degradation of gabapentin.

Gabapentin is known to undergo intramolecular cyclization to form a lactam (gaba-L) with concomitant loss of water. Gabapentin was milled in a planetary mill for 15-60 min. Unmilled and milled gabapentin were stored at 50°C with relative humidity ranged between 5% and 90%.

3-Methylglutaric acid as a 13C solid-state NMR standard.

The calibration of a solid-state NMR spectrometer requires setting the magic angle, setting the reference and decoupler frequencies, ensuring that the magnetic field is homogeneous across the sample volume, optimizing the signal-to-noise ratio, determining the pi/2 pulse durations, and optimizing the Hartman-Hahn matching condition. Each task has one or more widely accepted standards, such as potassium bromide for setting the magic angle, adamantane for optimizing magnet homogeneity, and hexamethylbenzene or glycine for measuring the signal-to-noise ratio. We show that all of these tasks can be performed using 3-methylglutaric acid (MGA).

Solid-state NMR spectra and long intradimer bonds in the pi-[TCNE]22- dianion.

The principal (13)C chemical-shift values for the pi-[TCNE](2)(2-) dimer anion within an array of counterions have been measured to understand better the electronic structure of these atypical chemical species in several related TCNE-based structures. The structure of pi-[TCNE](2)(2-) is unusual as it contains two very long C-C bond lengths (ca. 2.

Investigation of solid-state NMR line widths of ibuprofen in drug formulations.

Solid-state nuclear magnetic resonance spectroscopy (SSNMR) line widths were measured for various ibuprofen preparations, including crystallization from different solvents (acetone, acetonitrile, methanol), melt-quenching, manual grinding, cryogrinding, compacting, and by blending with various excipients. Ibuprofen recrystallized from acetonitrile exhibited broader lines than ibuprofen recrystallized from either acetone or methanol. Manually ground ibuprofen had SSNMR line widths that were indistinguishable from the commercial sample, but cryoground ibuprofen had larger line widths than either.

CB11Me11 boronium ylides: carba-closo-dodecaboranes with a naked boron vertex.

In pentane solution, 2 equiv of the icosahedral CB(11)Me(12)(*) radical cleaves the Si-Si bond of hexaalkyldisilanes by boron to silicon methyl transfer with formation of 2 equiv of methyltrialkylsilanes. The loss of a methyl radical converts the CB(11)Me(12)(*) radical into an internally charge-compensated "boronium ylide" CB(11)Me(11) with a naked vertex, which can be formally viewed as a deprotonated hypercloso carborane. It has been isolated as an air-sensitive solid, stable only below approximately -60 degrees C.

Multiple-sample probe for solid-state NMR studies of pharmaceuticals.

Solid-state NMR spectroscopy (SSNMR) is an extremely powerful technique for the analysis of pharmaceutical dosage forms. A major limitation of SSNMR is the number of samples that can be analyzed in a given period of time. A solid-state magic-angle spinning (MAS) probe that can simultaneously acquire up to seven SSNMR spectra is being developed to increase throughput/signal-to-noise ratios.

Metal cation-methyl interactions in CB11Me12(-) salts of Me3Ge+, Me3Sn+, and Me3Pb+.

Oxidation of Me(6)M(2) (M = Ge, Sn) and Me(4)Pb with the CB(11)Me(12)(*) radical in alkane solvents produced the insoluble salts Me(3)M(+)CB(11)Me(12)(-), characterized by CP-MAS NMR and EXAFS. The cations interact with methyl groups of CB(11)Me(12)(-) with coordination strength increasing from Pb to Ge. Density functional theory (DFT) calculations for the isolated ion pairs, Me(3)M(+)CB(11)Me(12)(-) (M = Ge, Sn), revealed three isomers with the cation above methyl 2, 7, or 12, and not above a BB edge or a BBB triangle.

2,4-dimethoxybenzoic acid and 2,5-dimethoxybenzoic acid.

The title compounds (both C(9)H(10)O(4)) have nearly planar structures, and the methyl and/or carboxylic acid groups lie out of the molecular plane, as dictated by steric interactions. 2,5-Dimethoxybenzoic acid (2,5-DMBA) forms an unusual intramolecular hydrogen bond between the carboxylic acid group and the O atom of the methoxy group in the 2-position [O.O = 2.

Solid-state 15N NMR studies of tobacco leaves.

Nitrogen-containing compounds are one important class of constituents in tobacco because of various pharmacological and biological properties. Three types of tobacco leaves (burley, bright, and oriental) were studied using solid-state (15)N NMR cross polarization with magic-angle spinning, dipolar dephasing and five pi replicated magic angle turning (FIREMAT) experiments. The results show that burley tobacco leaves contain significantly more pyridinic nitrogen than that of bright or oriental tobacco leaves.

Stereochemical analysis by solid-state NMR: structural predictions in ambuic acid.

Relative stereochemistry is predicted for ambuic acid using a novel solid-state NMR approach. This NMR technique entails a comparison of measured shift tensor principal values with computed values for all diastereomers, allowing the selection of a best-fit structure. The proposed method extends previous solution NMR structural data by simultaneously modeling with high statistical probability hydrogen-bonding arrangements and molecular conformation at two positions.

13C NMR investigation of solid-state polymorphism in 10-deacetyl baccatin III.

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.

Modeling of Benzene Adsorption in Metal-Exchanged Zeolites by Calculation of Li Chemical Shifts.

A 1:1 complex between Li and benzene is formed when benzene is adsorbed into a Li-exchanged zeolite. This was the result of calculations of the Li chemical shifts for several model complexes, including Li ⋅2 H O⋅C H (depicted). After C and H, Li is a further nucleus that can be studied to determine the structure and dynamics of complexes formed between organic species and metal cations in zeolites.