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Published on: April 19, 2021
Impact of Drug-Polymer Miscibility on Enthalpy Relaxation of Irbesartan Amorphous Solid Dispersions
Sonu Dalsania1, Jagadish Sharma1, Bhushan Munjal1
1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector - 67, S.A.S. Nagar, Mohali, Punjab, 160 062, India.
Purpose:
Drug-polymer miscibility has been proposed to play a critical role in physical stability of amorphous solid dispersions (ASDs). The purpose of the current work was to investigate the role of drug-polymer miscibility on molecular mobility, measured as enthalpy relaxation (ER) of amorphous irbesartan (IBS) in ASDs.
Methods:
Two polymers, i.e. polyvinylpyrrolidone K30 (PVP K30) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), were used to generate ASDs with 10% w/w of the polymer. Drug-polymer miscibility was determined using melting point depression (MPD) method. Molecular mobility was assessed from ER studies at a common degree of undercooling (DOU) (Tg - 13.0°C ± 0.5°C).
Results:
IBS exhibited higher miscibility in PVP K30 as compared to HPMCAS at temperature > 140°C. However, extrapolation of miscibility data to storage temperature (62°C) using Flory-Huggins (F-H) theory revealed a reversal of the trend. Miscibility of IBS was found to be higher in HPMCAS (2.6%) than PVP K30 (1.3%) at 62°C. Stretched relaxation time (τβ) of 17.4365 h and 7.0886 h was obtained for IBS-HPMCAS and IBS-PVP K30 ASDs, respectively.
Conclusion:
Miscibility of drug-polymer at storage temperature explained the behavior of the molecular mobility, while miscibility near the melting point provided a reverse trend. Results suggest that drug-polymer miscibility determined at temperatures higher than the storage temperature should be viewed cautiously.
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