High Sensitivity Detection of a Solubility Limiting Surface Transformation of Drug Particles by DNP SENS.

Viger-Gravel J, Pinon AC, Björgvinsdóttir S, Skantze U, Svensk Ankarberg A, Von Corswant C, Schantz S, Emsley L

J Pharm Sci 110 (6) 2452-2456 [2021-06-00; online 2021-01-06]

We investigate the presence of a surface species for the active pharmaceutical ingredient (API) AZD9496 with dynamic nuclear polarization surface enhanced nuclear spectroscopy (DNP SENS). We show that using DNP we can elucidate the presence of an amorphous form of the API at the surface of crystalline particles of the salt form. The amorphous form of the API has distinguishable 13C chemical shifts when compared to the salt form under various acidic conditions. The predominant form in frozen particles of AZD9496 is the salt, and we provide evidence to suggest that the amorphous layer at the surface is mainly made up of the dissociated free form.

Swedish NMR Centre (SNC) [Collaborative]

PubMed 33417900

DOI 10.1016/j.xphs.2020.12.037

Crossref 10.1016/j.xphs.2020.12.037

pii: S0022-3549(21)00004-6

Publications 9.5.0