Raw Material Variability and Its Impact on the Online Adaptive Control of Cohesive Powder Blend Homogeneity Using NIR Spectroscopy

Guolin Shi,Yanjiang Qiao,Jing Fu,Zhaozhou Lin,Chan Yang,Xinyuan Shi,Shengyun Dai,Bing Xu,Zhiqiang Zhang

doi:10.3390/pr7090568

Abstract

It is significant to analyze the blend homogeneity of cohesive powders during pharmaceutical manufacturing in order to provide the exact content of the active pharmaceutical ingredient (API) for each individual dose unit. In this paper, an online monitoring platform using an MEMS near infrared (NIR) sensor was designed to control the bin blending process of cohesive powders. The state of blend homogeneity was detected by an adaptive algorithm, which was calibration free. The online control procedures and algorithm’s parameters were fine-tuned through six pilot experiments and were successfully transferred to the industrial production. The reliability of homogeneity detection results was validated by 16 commercial scale experiments using 16 kinds of natural product powders (NPPs), respectively. Furthermore, 19 physical quality attributes of all NPPs and the excipient were fully characterized. The blending end time was used to denote the degree of difficulty of blending. The empirical relationships between variability of NPPs and the blending end time were captured by latent variable modeling. The critical material attributes (CMAs) affecting the blending process were identified as the particle shape and flowability descriptors of cohesive powders. Under the framework of quality by design (QbD) and process analytical technology (PAT), the online NIR spectroscopy together with the powder characterization facilitated a deeper understanding of the mixing process.

Highlights

The powder mixing process is one of the key processes for the production of pharmaceutical oral solid preparations
The blending process in the preparation of diverse natural product powders with typically cohesive characteristics was taken as the research object
The MEMS near infrared (NIR) sensor combined with typically cohesive characteristics was taken as the research object

Summary

Introduction

The powder mixing process is one of the key processes for the production of pharmaceutical oral solid preparations. In order to effectively monitor the CQA and system dynamic changes of the mixing process, the pharmaceutical industry is encouraged to adopt new process analysis methods under the American Food and Drug. Administration (FDA) guidance on process analytical technology (PAT) [6]. Many techniques such as near infrared (NIR) spectroscopy [7,8,9,10], Raman spectroscopy (RS) [3,11] and chemical imaging (CI) [12,13] have been reported on determination of BU. Compared with the stratified sampling and offline analysis mode, these online methods enable high frequency sampling, multi-point detection, real time and non-invasive process control, as well as increased production efficiency and reduced operation costs

Methods

Results

Conclusion