Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
J Pharm Sci. 2019 Dec;108(12):3848-3858. doi: 10.1016/j.xphs.2019.09.013. Epub 2019 Sep 19.
The study aims to characterize the structural relaxation times of quench-cooled co-amorphous systems using Kohlrausch-Williams-Watts (KWW) and to correlate the relaxation data with the onset of crystallization. Comparison was also made between the relaxation times obtained by KWW and the width of glass transition temperature (ΔT) methods (simple and quick). Differential scanning calorimetry, Fourier-transformed infrared spectroscopy, and polarized light microscopy were used to characterize the systems. Results showed that co-amorphous systems yielded a single T and ΔC, suggesting the binary mixtures exist as a single amorphous phase. A narrow step change at T indicates the systems were fragile glasses. In co-amorphous nap-indo and para-indo, experimental Ts were in good agreement with the predicted T. However, the T of co-amorphous nap-cim and indo-cim were 20°C higher than the predicted T, possibly due to stronger molecular interactions. Structural relaxation times below the experimental T were successfully characterized using the KWW and ΔT methods. The comparison plot showed that KWW data are directly proportional to the ½ power of ΔT data, after adjusting for a small offset. A moderate positive correlation was observed between the onset of crystallization and the KWW data. Structural relaxation times may be useful predictor of physical stability of co-amorphous systems.
本研究旨在使用 Kohlrausch-Williams-Watts（KWW）来描述淬火冷却共无定形系统的结构弛豫时间，并将弛豫数据与起始结晶相关联。还比较了 KWW 和玻璃化转变温度（ΔT）方法（简单快速）获得的弛豫时间之间的差异。差示扫描量热法、傅里叶变换红外光谱法和偏光显微镜用于系统表征。结果表明，共无定形系统产生单一的 T 和 ΔC，表明二元混合物存在单一的无定形相。T 处的窄阶跃变化表明系统是脆弱的玻璃。在 nap-indo 和 para-indo 的共无定形中，实验 Ts 与预测 T 吻合较好。然而，nap-cim 和 indo-cim 的共无定形的 T 比预测的 T 高 20°C，可能是由于更强的分子相互作用。使用 KWW 和 ΔT 方法成功地对实验 T 以下的结构弛豫时间进行了表征。比较图表明，调整小偏移后，KWW 数据与 ΔT 数据的 1/2 次幂成正比。在结晶开始时观察到与 KWW 数据呈中度正相关。结构弛豫时间可能是共无定形系统物理稳定性的有用预测指标。
