Sonu Dalsania1, Jagadish Sharma1, Bhushan Munjal1, Arvind K Bansal2. 1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector - 67, S.A.S. Nagar, Mohali, Punjab, 160 062, India. 2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector - 67, S.A.S. Nagar, Mohali, Punjab, 160 062, India. akbansal@niper.ac.in.
Abstract
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.
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.
Entities:
Keywords:
Gibb’s free energy of mixing; amorphous solid dispersion; enthalpy relaxation; irbesartan; miscibility
Authors: Dwayne T Friesen; Ravi Shanker; Marshall Crew; Daniel T Smithey; W J Curatolo; J A S Nightingale Journal: Mol Pharm Date: 2008 Nov-Dec Impact factor: 4.939