TY - JOUR
T1 - Impact of Drug-Polymer Miscibility on Enthalpy Relaxation of Irbesartan Amorphous Solid Dispersions
AU - Dalsania, Sonu
AU - Sharma, Jagadish
AU - Munjal, Bhushan
AU - Bansal, Arvind K.
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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) (T g − 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 (τ β ) 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.
AB - 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) (T g − 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 (τ β ) 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.
KW - amorphous solid dispersion
KW - enthalpy relaxation
KW - Gibb’s free energy of mixing
KW - irbesartan
KW - miscibility
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U2 - 10.1007/s11095-017-2296-y
DO - 10.1007/s11095-017-2296-y
M3 - Article
C2 - 29368174
AN - SCOPUS:85041012024
SN - 0724-8741
VL - 35
JO - Pharmaceutical research
JF - Pharmaceutical research
IS - 2
M1 - 29
ER -