Abstract：
The appearance of an extrudate formulation was monitored during hot-melt extrusion (HME) continuous manufacturing over 3 days. The formulation matrix consisted of a polymeric component, copovidone, and a low molecular weight surfactant, polysorbate 80. Based on studies prior to the continuous manufacturing, the desired appearance of the target extrudate is translucent. Although process parameters such as feed rate and screw speed were fixed during the continuous manufacturing, the extrudate appearance changed over time from turbid to translucent. For root-cause investigation, the extrudates were analyzed offline by differential scanning calorimetry (DSC) and advanced polymer chromatography (APC™). Although the polysorbate 80 content of both turbid and translucent extrudates was within target, the glass transition temperature of the turbid extrudate was 2 °C above expected value. The observed turbidity was traced to lot-to-lot variability of the polysorbate 80 used in the continuous manufacturing, where APC™ analysis revealed that the relative content of the low molecular weight component varied from 23% to 27% in correlation with the evolution from turbid to translucent extrudates. This work stresses the importance of taking feeding material variability into account during continuous manufacturing.
摘要：
在三天的热熔挤出(HME)连续制造期间监测挤出物制剂的外观。制剂基质由聚合物组分组成，共聚维酮,和低分子量表面活性剂，聚山梨酯80.根据连续制造之前的研究，目标挤出物的所需外观是半透明的。尽管在连续制造过程中，诸如进给速度和螺杆速度等工艺参数是固定的，挤出物外观随时间从浑浊变为半透明。对于根本原因调查，通过差示扫描量热法(DSC)和高级聚合物色谱法(APC™)离线分析挤出物。尽管浑浊和半透明挤出物的聚山梨酯80含量均在目标范围内，混浊挤出物的玻璃化转变温度为高于预期值2°C。观察到的浊度可追溯到连续制造中使用的聚山梨酯80的批次间差异。其中APC™分析揭示低分子量组分的相对含量从23%变化到27%,与从浑浊到半透明挤出物的演变相关。这项工作强调了在连续制造过程中考虑进料可变性的重要性。
