Fluidised bed granulation of two APIs:QbD approach and development of a NIR in-line monitoring method  

作　　者：Alexandru Gavan Sonia Iurian Tibor Casian Alina Porfire Sebastian Porav Ioana Voina Alexandru Oprea Ioan Tomuta 

机构地区：[1]Faculty of Pharmacy,Iuliu Hatieganu University of Medicine and Pharmacy,Cluj-Napoca 400012,Romania [2]National Institute for Research and Development of Isotopic and Molecular Technologies,Cluj-Napoca 400293,Romania [3]S.C.Laropharm SRL,Bragadiru 077025,Romania

出　　处：《Asian Journal of Pharmaceutical Sciences》2020年第4期506-517,共12页亚洲药物制剂科学（英文）

基　　金：This work was supported by the Romanian National Authority for Scientific Research and Innovation,CNCS-UEFISCDI[project number PN-III-P2-2.1-BG-2016-0201].

摘　　要：The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.

关 键 词：Quality by design Design space Risk assessment Process analytical technology Fluid bed granulation MicroNIR 

分 类 号：TG1[金属学及工艺—金属学]