Accelerated stability modeling of recrystallization from amorphous solid Dispersions: A Griseofulvin/HPMC-AS case study.

Autor: Leon AS; Level 2, Block C3, Maple Science Park, Qixia District, Nanjing 210048 China., Waterman KC; 688 East Main Street, Branford, CT 06405, USA., Wang G; Level 2, Block C3, Maple Science Park, Qixia District, Nanjing 210048 China., Wang L; Level 2, Block C3, Maple Science Park, Qixia District, Nanjing 210048 China. Electronic address: likun.wang@haiwei-tech.com., Cai T; China Pharmaceutical University, 24 Tongjiaxiang Road, Nanjing 210009 China., Zhang X; 99 HengGuang Road, Nanjing Development Zone, Nanjing 210038 China.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 May 25; Vol. 657, pp. 124189. Date of Electronic Publication: 2024 May 01.
DOI: 10.1016/j.ijpharm.2024.124189
Abstrakt: Amorphous solid dispersions (ASDs) represent an important approach for enhancing oral bioavailability for poorly water soluble compounds; however, assuring that these ASDs do not recrystallize to a significant extent during storage can be time-consuming. Therefore, various efforts have been undertaken to predict ASD crystallization levels with kinetic models. However, only limited success has been achieved due to limits on crystal content quantification methods and the complexity of crystallization kinetics. To increase the prediction accuracy, the accelerated stability assessment program (ASAP), employing isoconversion (time to hit a specification limit) and a modified Arrhenius approach, are employed here for predictive shelf-life modeling. In the current study, a model ASD was prepared by spray drying griseofulvin and HPMC-AS-LF. This ASD was stressed under a designed combinations of temperature, relative humidity and time with the conditions set to ensure stressing was carried out below the glass transition temperature (T g ) of the ASD. Crystal content quantification method by X-ray powder diffraction (XRPD) with sufficient sensitivity was developed and employed for stressed ASD. Crystallization modeling of the griseofulvin ASD using ASAPprime® demonstrated good agreement with long-term (40 °C/75 %RH) crystallinity levels and support the use of this type of accelerated stability studies for further improving ASD shelf-life prediction accuracy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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