Understanding the Effect of Nucleation in Amorphous Solid Dispersions through Time–Temperature Transformation
- Rahul Lalge
Rahul LalgeDepartment of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-177 WDH, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, United StatesMore by Rahul Lalge
- ,
- N. S. Krishna Kumar
N. S. Krishna KumarDepartment of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-177 WDH, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, United StatesMore by N. S. Krishna Kumar
- , and
- Raj Suryanarayanan*
Raj Suryanarayanan*Email: [email protected]. Phone: 612-624-9626. Fax: 612-626-2125.Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-177 WDH, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, United StatesMore by Raj Suryanarayanan
Abstract
In an earlier investigation, the critical cooling rate to prevent drug crystallization (CRcrit) during the preparation of nifedipine (NIF) amorphous solid dispersions (ASDs) was determined through a time–temperature transformation (TTT) diagram (Lalge et al. Mol. Pharmaceutics 2023, 20 (3), 1806–1817). The current study aims to use the TTT diagram to determine the critical cooling rate to prevent drug nucleation (CRcrit N) during the preparation of ASDs. ASDs were prepared with each polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS). The dispersions were first stored under conditions promoting nucleation and then heated to the temperature that favors crystallization. The crystallization onset time (tC) was determined by differential scanning calorimetry and synchrotron X-ray diffractometry. TTT diagrams for nucleation were generated, which provided the critical nucleation temperature (50 °C) and the critical cooling rate to avoid nucleation (CRcrit N). The strength of the drug–polymer interactions as well as the polymer concentration affected the CRcrit N, with PVP having a stronger interaction than HPMCAS. The CRcrit of amorphous NIF was ∼17.5 °C/min. The addition of a 20% w/w polymer resulted in CRcrit of ∼0.05 and 0.2 °C/min and CRcrit N of ∼4.1 and 8.1 °C/min for the dispersions prepared with PVP and HPMCAS, respectively.
Cited By
This article has not yet been cited by other publications.