Solid state nuclear magnetic resonance studies of hydroxypropylmethylcellulose acetyl succinate polymer, a useful carrier in pharmaceutical solid dispersions

© 2019 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.

Bibliographische Detailangaben
Veröffentlicht in:Magnetic resonance in chemistry : MRC. - 1985. - 58(2020), 11 vom: 16. Nov., Seite 1036-1048
1. Verfasser: Pugliese, Andrea (VerfasserIn)
Weitere Verfasser: Hawarden, Lucy E, Abraham, Anuji, Tobyn, Michael, Blanc, Frédéric
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Magnetic resonance in chemistry : MRC
Schlagworte:Journal Article 13C HPMC-AS amorphous solid dispersion hydroxypropylmethylcellulose solid-state NMR spectroscopy Carbon Isotopes Polymers hydroxypropylmethylcellulose acetate succinate 71138-97-1 mehr... Methylcellulose 9004-67-5 Carbon-13 FDJ0A8596D
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520 |a © 2019 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd. 
520 |a Hydroxypropylmethylcellulose (HPMC) acetyl succinate (HPMC-AS) is a key polymer used for the enablement of amorphous solid dispersions (ASDs) in oral solid dosage forms. Choice of the appropriate grade within the material is often made empirically by the manufacturer of small-scale formulations, followed by extensive real time stability. A key factor in understanding and predicting the performance of an ASD is related to the presence of hydrogen (or other) bonds between the polymer and active pharmaceutical ingredient (API), which will increase stability over the parameters captured by miscibility and predicted by the Gordon-Taylor equation. Solid state nuclear magnetic resonance (NMR) is particularly well equipped to probe spatial proximities, for example, between polymer and API; however, in the case of HPMC-AS, these interactions have been sometimes difficult to identity as the carbon-13 NMR spectra assignment is yet to be firmly established. Using feedstock, selectively substituted HPMC polymers, and NMR editing experiments, we propose here a comprehensive understanding of the chemical structure of HPMC-AS and a definitive spectral assignment of the 13 C NMR spectra of this polymer. The NMR data also capture the molar ratios of the acetate and succinate moieties present in HPMC-AS of various grades without the need for post treatment required by chromatography methods commonly use in pharmacopoeia. This knowledge will allow the prediction and measurement of interactions between polymers and APIs and therefore a rational choice of polymer grade to enhance the solid state stability of ASDs 
650 4 |a Journal Article 
650 4 |a 13C 
650 4 |a HPMC-AS 
650 4 |a amorphous solid dispersion 
650 4 |a hydroxypropylmethylcellulose 
650 4 |a solid-state NMR spectroscopy 
650 7 |a Carbon Isotopes  |2 NLM 
650 7 |a Polymers  |2 NLM 
650 7 |a hydroxypropylmethylcellulose acetate succinate  |2 NLM 
650 7 |a 71138-97-1  |2 NLM 
650 7 |a Methylcellulose  |2 NLM 
650 7 |a 9004-67-5  |2 NLM 
650 7 |a Carbon-13  |2 NLM 
650 7 |a FDJ0A8596D  |2 NLM 
700 1 |a Hawarden, Lucy E  |e verfasserin  |4 aut 
700 1 |a Abraham, Anuji  |e verfasserin  |4 aut 
700 1 |a Tobyn, Michael  |e verfasserin  |4 aut 
700 1 |a Blanc, Frédéric  |e verfasserin  |4 aut 
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