Pugliese, Andrea, Toresco, Michael, McNamara, Daniel, Iuga, Dinu, Abraham, Anuji, Tobyn, Michael, Hawarden, Lucy E and Blanc, Frederic 
ORCID: 0000-0001-9171-1454
(2021)
Drug-Polymer Interactions in Acetaminophen/ Hydroxypropylmethylcellulose Acetyl Succinate Amorphous Solid Dispersions Revealed by Multidimensional Multinuclear Solid-State NMR Spectroscopy.
MOLECULAR PHARMACEUTICS, 18 (9).
pp. 3519-3531.
ISSN 1543-8384, 1543-8392
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MS ID mp-2021-00427e.R1 - reviewed manuscript.pdf - Author Accepted Manuscript Download (1MB) | Preview |
Abstract
The bioavailability of insoluble crystalline active pharmaceutical ingredients (APIs) can be enhanced by formulation as amorphous solid dispersions (ASDs). One of the key factors of ASD stabilization is the formation of drug-polymer interactions at the molecular level. Here, we used a range of multidimensional and multinuclear nuclear magnetic resonance (NMR) experiments to identify these interactions in amorphous acetaminophen (paracetamol)/hydroxypropylmethylcellulose acetyl succinate (HPMC-AS) ASDs at various drug loadings. At low drug loading (<20 wt %), we showed that <sup>1</sup>H-<sup>13</sup>C through-space heteronuclear correlation experiments identify proximity between aromatic protons in acetaminophen with cellulose backbone protons in HPMC-AS. We also show that <sup>14</sup>N-<sup>1</sup>H heteronuclear multiple quantum coherence (HMQC) experiments are a powerful approach in probing spatial interactions in amorphous materials and establish the presence of hydrogen bonds (H-bond) between the amide nitrogen of acetaminophen with the cellulose ring methyl protons in these ASDs. In contrast, at higher drug loading (40 wt %), no acetaminophen/HPMC-AS spatial proximity was identified and domains of recrystallization of amorphous acetaminophen into its crystalline form I, the most thermodynamically stable polymorph, and form II are identified. These results provide atomic scale understanding of the interactions in the acetaminophen/HPMC-AS ASD occurring via H-bond interactions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | acetaminophen (paracetamol), hydroxypropylmethylcellulose acetyl succinate (HPMC-AS), amorphous solid dispersion, solid-state NMR, drug-polymer interactions, multidimensional NMR |
| Divisions: | Faculty of Science and Engineering > School of Physical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 Aug 2021 07:23 |
| Last Modified: | 07 Dec 2024 22:16 |
| DOI: | 10.1021/acs.molpharmaceut.1c00427 |
| Open Access URL: | https://pubs.acs.org/doi/10.1021/acs.molpharmaceut... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3133272 |
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