F. Hoffmann-La Roche Ltd., pRED Small Molecule Research, Discovery Technologies, 4070 Basel, Switzerland.
Pharm Res. 2013 Aug;30(8):2010-22. doi: 10.1007/s11095-013-1045-0. Epub 2013 May 15.
To verify the robustness and fundamental value of Atomic Force Microscopy (AFM) and AFM-based assays to rapidly examine the molecular homogeneity and physical stability of amorphous solid dispersions on Hot-Melt-Extrudates.
Amorphous solid dispersions were prepared with a Hot-Melt Extruder (HME) and profiled by Raman Microscopy and AFM following a sequential analytical routine (Multi-Scale-Imaging-of-Miscibiliy (MIMix)). Extrudates were analyzed before and after incubation at elevated temperature and humidity. The data were compared with published results as collected on miniaturized melt models. The value of molecular phase separation rates for long term stability prediction was assessed.
Data recorded on the extrudates are consistent with those published, and they can be compared side by side. Such direct data comparisons allow the identification of possible sources of extrudate heterogeneities. The surface roughness analysis of fracture-exposed interfaces is a novel quantitative way to trace on the nanometer scale the efficiencies of differently conducted HME-processes. Molecular phase separation rates are shown to be relevant for long term stability predictions.
The AFM-based assessment of API:excipient combinations is a robust method to rapidly identify miscible and stable solid dispersions in a routine manner. It provides a novel analytical tool for the optimization of HME processes.
验证原子力显微镜（AFM）和基于 AFM 的分析方法的稳健性和基本价值，以快速检查热熔挤出物中无定形固体分散体的分子均一性和物理稳定性。
采用热熔挤出机（HME）制备无定形固体分散体，并采用拉曼显微镜和 AFM 按照顺序分析程序（多尺度可混溶性成像（MIMix））进行分析。在高温高湿条件下孵育前后对挤出物进行分析。将数据与在小型熔融模型上收集的已发表结果进行比较。评估分子相分离速率对于长期稳定性预测的价值。
挤出物上记录的数据与已发表的数据一致，可以并排比较。这种直接的数据比较可以识别挤出物异质性的可能来源。对断裂暴露界面的表面粗糙度分析是一种新颖的定量方法，可以在纳米尺度上跟踪不同进行的 HME 过程的效率。分子相分离速率被证明与长期稳定性预测相关。
基于 AFM 的 API：赋形剂组合评估是一种快速识别常规方法中可混溶和稳定的固体分散体的稳健方法。它为 HME 工艺的优化提供了一种新的分析工具。
