Islam Muhammad T, Scoutaris Nikolaos, Maniruzzaman Mohammed, Moradiya Hiren G, Halsey Sheelagh A, Bradley Michael S A, Chowdhry Babur Z, Snowden Martin J, Douroumis Dennis
Faculty of Engineering and Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent ME4 4TB, UK.
ThermoFisher Scientific, Stafford House, Boundary Way, Hemel Hempstead HP2 7GE, UK.
Eur J Pharm Biopharm. 2015 Oct;96:106-16. doi: 10.1016/j.ejpb.2015.06.021. Epub 2015 Jul 21.
The aim of the work reported herein was to implement process analytical technology (PAT) tools during hot melt extrusion (HME) in order to obtain a better understanding of the relationship between HME processing parameters and the extruded formulations. For the first time two in-line NIR probes (transmission and reflectance) have been coupled with HME to monitor the extrusion of the water insoluble drug indomethacin (IND) in the presence of Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion monitoring of sheets, produced via a specially designed die, was conducted at various drug/polymer ratios and processing parameters. Characterisation of the extruded transparent sheets was also undertaken by using DSC, XRPD and Raman mapping. Analysis of the experimental findings revealed the production of molecular solutions where IND is homogeneously blended (ascertained by Raman mapping) in the polymer matrices, as it acts as a plasticizer for both hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the screw speed used in HME affects the recorded spectra but not the homogeneity of the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets displayed rapid dissolution rates with 80% and 30% of the IND being released, respectively within the first 20min.
本文所报道工作的目的是在热熔挤出（HME）过程中应用过程分析技术（PAT）工具，以便更好地理解HME加工参数与挤出制剂之间的关系。首次将两个在线近红外探头（透射和反射）与HME联用，以监测在存在Soluplus（SOL）或聚乙烯吡咯烷酮VA64亲水性聚合物的情况下水不溶性药物吲哚美辛（IND）的挤出过程。通过专门设计的模具对片材进行在线挤出监测，监测在不同药物/聚合物比例和加工参数下进行。还通过差示扫描量热法（DSC）、X射线粉末衍射（XRPD）和拉曼映射对挤出的透明片材进行表征。对实验结果的分析表明，形成了分子溶液，其中IND在聚合物基质中均匀混合（通过拉曼映射确定），因为它对两种亲水性聚合物都起到增塑剂的作用。对记录的近红外信号进行主成分分析（PCA）表明，HME中使用的螺杆速度会影响记录的光谱，但不会影响聚合物片中包埋药物的均匀性。IND/VA64和IND/SOL挤出片材显示出快速的溶解速率，分别在最初20分钟内释放了80%和30%的IND。
