Study of powder blends properties and behaviors for pharmaceutical continuous manufacturing
Creators: name: Li, Jingzhe
Publisher: name: No Publisher Supplied
Year: 2022

description: Pharmaceutical manufacturing is experiencing unprecedented scientific and technological innovation in recent decades. Continuous manufacturing (CM) is an emerging technology which attracts major pharmaceutical companies around the world. Researchers from academia and industry have reported enormous advantages, including fast product development, using less materials, close-loop process control, and better product quality. Also, the US Food and Drug Administration (FDA) has provided regulatory support for enhancing the implementation of the concepts of “Quality by Design” (QbD) into CM processes. The transfer from step-by-step batch manufacturing to closed-loop control in continuous manufacturing should base on the QbD concept that product’s quality should be built into the product based on thorough understanding of the product and process. As continuous pharmaceutical manufacturing continues to developed and gain acceptance, one of the main goals will be to understand of material behavior and process dynamics of the manufacturing systems associated with this platform. In this work, methodologies for analyzing properties and behavior of intermediates materials and final product, and for predicting process performance, were developed.The first aim of this work is to investigate the influence of pharmaceutical process parameters on blend properties. The batch manufacturing route has a different mixing mechanism from the continuous route. To find the correlation between these two different blending processes, studies include using statistical analysis to discuss the effect of shear strain on blend properties. Also, the feed frame inside the tablet press will introduce extra shear strain to the blends. The rotation speed of feed frame will consider as another variable in the first aim. Tablet properties will be other criteria to define the difference between the two routes.To quantitatively determine the shear strain of the continuous process, the PAT helps with online monitoring of blend uniformity to study the residence time distribution (RTD) of powder in the continuous system. The second aim will evaluate the performance of Raman and Near IR spectroscopy in terms of accuracy, precision, operating range, measurement frequency, placement, and reliability. To explore PAT’s limitation, a new technic of spatially resolved NIR in the third aim is applied on predicting low dose formulation as 0.3% (w/w) active pharmaceutical component (API) in tablet press feed frame. Through utilizing PAT, the RTD of each unit process will be studied in the fourth aim. In particular, the retention time of powder in the transition area between each pharmaceutical unit operations will be analyzed since the main difference between the many different manufacturing lines is transition zones. Ultimately, this work will support innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance by implementing advanced process control strategies to investigate the upstream continuous pharmaceutical manufacturing design space.