TY - JOUR
T1 - PC-SAFT-Assisted Design of Antisolvent Naproxen Crystallization in the Presence of Polymers
AU - Petza Kloc, Amábille
AU - Anjum, Fatima
AU - Wessner, Maximilian
AU - Hudson, Sarah
AU - Fernandes, Philippe
AU - De Witte, Bruno
AU - Sadowski, Gabriele
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/4/17
Y1 - 2024/4/17
N2 - The solubility of naproxen in aqueous solutions containing polyvinylpyrrolidone (PVP) or poly(vinylpyrrolidone-co-vinylacetate) (PVPVA64), was predicted using the thermodynamic model PC-SAFT. The predictions showed a lower solubility of naproxen in PVP solutions compared to PVPVA64 solutions, and the results were confirmed experimentally. Based on this data and their modeling, suitable process conditions for a solvent/antisolvent crystallization of naproxen in the presence of one of the two polymers were identified to produce long-acting injectable suspensions. Naproxen crystallization experiments were conducted by means of antisolvent precipitation from a supersaturated ethanol solution using water as antisolvent. PC-SAFT predictions were used to identify the initial naproxen concentration in solvent solutions, the optimum antisolvent-to-solvent stream ratio, the final naproxen loading, and the theoretical crystal yield, thus assisting the design of the crystallization experiments. The maximum absolute deviation between the experimental crystal yield and that obtained from PC-SAFT predictions was about 1.4%. The size of naproxen particles obtained from the crystallization experiments was less than 20 μm, which is in accordance with the particle size required for long-acting injectable suspensions.
AB - The solubility of naproxen in aqueous solutions containing polyvinylpyrrolidone (PVP) or poly(vinylpyrrolidone-co-vinylacetate) (PVPVA64), was predicted using the thermodynamic model PC-SAFT. The predictions showed a lower solubility of naproxen in PVP solutions compared to PVPVA64 solutions, and the results were confirmed experimentally. Based on this data and their modeling, suitable process conditions for a solvent/antisolvent crystallization of naproxen in the presence of one of the two polymers were identified to produce long-acting injectable suspensions. Naproxen crystallization experiments were conducted by means of antisolvent precipitation from a supersaturated ethanol solution using water as antisolvent. PC-SAFT predictions were used to identify the initial naproxen concentration in solvent solutions, the optimum antisolvent-to-solvent stream ratio, the final naproxen loading, and the theoretical crystal yield, thus assisting the design of the crystallization experiments. The maximum absolute deviation between the experimental crystal yield and that obtained from PC-SAFT predictions was about 1.4%. The size of naproxen particles obtained from the crystallization experiments was less than 20 μm, which is in accordance with the particle size required for long-acting injectable suspensions.
UR - http://www.scopus.com/inward/record.url?scp=85189564618&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.4c00143
DO - 10.1021/acs.cgd.4c00143
M3 - Article
AN - SCOPUS:85189564618
SN - 1528-7483
VL - 24
SP - 3419
EP - 3429
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 8
ER -