Probing Hydrogen Bonding in Cocrystals and Amorphous Dispersions Using 14N鈥?sup>1H HMQC Solid-State NMR

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• 作者：Andrew S. Tatton ; Tran N. Pham ; Frederick G. Vogt ; Dinu Iuga ; Andrew J. Edwards ; Steven P. Brown
• 刊名：Molecular Pharmaceutics
• 出版年：2013
• 出版时间：March 4, 2013
• 年：2013
• 卷：10
• 期：3
• 页码：999-1007
• 全文大小：349K
• 年卷期：v.10,no.3(March 4, 2013)
• ISSN：1543-8392

文摘

Cocrystals and amorphous solid dispersions have generated interest in the pharmaceutical industry as an alternative to more established solid delivery forms. The identification of intermolecular hydrogen bonding interactions in a nicotinamide palmitic acid cocrystal and a 50% w/w acetaminophen鈥損olyvinylpyrrolidone solid dispersion are reported using advanced solid-state magic-angle spinning (MAS) NMR methods. The application of a novel ¹⁴N鈥?sup>1H HMQC experiment, where coherence transfer is achieved via through-space couplings, is shown to identify specific hydrogen bonding motifs. Additionally, ¹H isotropic chemical shifts and ¹⁴N electric field gradient (EFG) parameters, both accessible from ¹⁴N鈥?sup>1H HMQC experiments, are shown to be sensitive to changes in hydrogen bonding geometry. Numerous indicators of molecular association are accessible from this experiment, including NH cross-peaks occurring from intermolecular hydrogen bonds and changes in proton chemical shifts or electric field gradient parameters. First-principles calculations using the GIPAW approach that yield accurate estimates of isotropic chemical shifts, and EFG parameters were used to assist in assignment. It is envisaged that ¹⁴N鈥?sup>1H HMQC solid state NMR experiments could become a valuable screening technique of solid delivery forms in the pharmaceutical industry.

Keywords:

pharmaceutical cocrystals; amorphous solid dispersions; molecular dispersions; glass solution; nanosuspension; solid-state NMR; ¹⁴N鈭?sup>1H HMQC (heteronuclear multiple-quantum correlation); ¹⁴N EFG (electric field gradient); GIPAW (gauge-including projector-augmented wave)