Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector - 67, S.A.S. Nagar, Mohali, Punjab, 160 062, India.
Pharm Res. 2018 Jan 9;35(2):29. doi: 10.1007/s11095-017-2296-y.
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.
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 - 13.0°C ± 0.5°C).
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) of 17.4365 h and 7.0886 h was obtained for IBS-HPMCAS and IBS-PVP K30 ASDs, respectively.
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.
药物-聚合物混溶性被认为在无定形固体分散体（ASD）的物理稳定性中起着关键作用。本研究的目的是研究药物-聚合物混溶性对无定形厄贝沙坦（IBS）在 ASD 中分子迁移率（以焓弛豫（ER）测量）的影响。
使用聚维酮 K30（PVP K30）和醋酸羟丙甲纤维素琥珀酸酯（HPMCAS）两种聚合物，以 10%w/w 的聚合物生成 ASD。使用熔点降低（MPD）法测定药物-聚合物的混溶性。在共同过冷度（DOU）（T-13.0°C±0.5°C）下进行 ER 研究来评估分子迁移率。
IBS 在高于 140°C 的温度下与 PVP K30 相比表现出更高的混溶性，但使用 Flory-Huggins（F-H）理论将混溶性数据外推到储存温度（62°C）时，趋势发生逆转。在 62°C 时，IBS 在 HPMCAS（2.6%）中的混溶性高于 PVP K30（1.3%）。IBS-HPMCAS 和 IBS-PVP K30 ASD 的拉伸弛豫时间（τ）分别为 17.4365 h 和 7.0886 h。
储存温度下药物-聚合物的混溶性解释了分子迁移率的行为，而接近熔点时的混溶性提供了相反的趋势。结果表明，应谨慎看待高于储存温度下测定的药物-聚合物混溶性。
