College of Pharmacy, The University of Texas at Austin, Austin, TX, USA; DisperSol Technologies, Georgetown, TX, USA.
J Pharm Pharmacol. 2014 Feb;66(2):204-17. doi: 10.1111/jphp.12106. Epub 2013 Jul 31.
The use of corotating twin screw hot-melt extruders to prepare amorphous drug/polymer systems has become commonplace. As small molecule drug candidates exiting discovery pipelines trend towards higher MW and become more structurally complicated, the acceptable operating space shifts below the drug melting point. The objective of this research is to investigate the extrusion process space, which should be selected to ensure that the drug is solubilized in the polymer with minimal thermal exposure, is critical in ensuring the performance, stability and purity of the solid dispersion.
The properties of a model solid dispersion were investigated using both corotating and counter-rotating hot-melt twin-screw extruders operated at various temperatures and screw speeds. The solid state and dissolution performance of the resulting solid dispersions was investigated and evaluated in context of thermodynamic predictions from Flory-Huggins Theory. In addition, the residence time distributions were measured using a tracer, modelled and characterized.
The amorphous content in the resulting solid dispersions was dependent on the combination of screw speed, temperature and operating mode.
The counter-rotating extruder was observed to form amorphous solid dispersions at a slightly lower temperature and with a narrower residence time distribution, which also exhibited a more desirable shape.
使用同向双螺杆热熔挤出机来制备无定形药物/聚合物体系已经变得很常见。随着发现管道中的小分子药物候选物朝着更高的分子量和更复杂的结构发展，可接受的操作空间会转移到低于药物熔点以下。本研究的目的是研究挤出过程空间，为了确保药物在聚合物中溶解，同时最小化热暴露，这对于确保固体分散体的性能、稳定性和纯度至关重要。
使用同向和反向旋转热熔双螺杆挤出机在不同的温度和螺杆速度下对模型固体分散体的性能进行了研究。根据 Flory-Huggins 理论的热力学预测，研究并评估了所得固体分散体的固态和溶解性能。此外，使用示踪剂测量停留时间分布，并对其进行建模和表征。
所得固体分散体中的无定形含量取决于螺杆速度、温度和操作模式的组合。
观察到反向旋转挤出机能以稍低的温度和更窄的停留时间分布形成无定形固体分散体，其还表现出更理想的形态。
