Miscibility of amorphous solid dispersions: A rheological and solid-state NMR spectroscopy study

Miscibility is critical in the prediction of stability against crystallization of amorphous solid dispersions (ASDs) in the solid state. However, currently available approaches for its determination are limited by both theoretical and practical considerations. Recently, a rheological approach guided by the polymer overlap concentration (c*) has been proposed for miscibility quantification of ASDs [J. Pharm. Sci., 112 (2023) 204-212] and shown to be useful in predicting both accelerated and long term physical stability in the absence of moisture. However, this approach can only be performed at high temperatures (slightly above the melting temperature, Tm, of drugs), and little is known about the difference in miscibility between high and low temperatures (e.g., below the glass transition temperature, Tg). Here we compare the miscibility of nifedipine (NIF)/polyvinylpyrrolidone (PVP) ASDs as determined by the rheological approach at 175 degrees C ( 3 degrees C above Tm of NIF) and solid state NMR (ssNMR) 1H T1 and T1r relaxation times at -20 degrees C ( 66 degrees C below Tg of NIF). Our results indicate agreement between the two methods. For low molecular weight (Mw) PVP, T1r measurements are more consistent with the rheological approach, while T1 measurements are closer for relatively high Mw PVP. Our findings support the use of the c* based rheological approach for inferring miscibility of deeply cooled ASDs. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.