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

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.

Pharmaceutical application of multivariate modelling techniques: a review on the manufacturing of tablets

“…To effectively detect the CQAs and gain a deeper understanding of the change in dynamics of the mixing process, near-infrared (NIR) instruments are widely used PAT tools to monitor the blending process. 47,146–151 The application of Raman spectroscopy in a study of the mixing process has also been reported. 152–154 However, in order to obtain meaningful results, spectral data must be transformed by chemometrics.…”

“… 152–154 However, in order to obtain meaningful results, spectral data must be transformed by chemometrics. 47 Multivariate modeling approaches, which play an important role in translating spectral signals to BU, can be applied to monitor the mixing process.…”

Towards real time release testing of Shuxuening injection based on near infrared spectroscopy and accuracy profile

“…[16][17][18] NIR spectroscopy can provide accurate measurement in a simple and real-time way, and it has been successfully applied to quality control of Chinese medicine and Chinese herbal preparation manufacturing processes. [19][20][21][22][23] Once the NIR method is developed, methodology validation is a mandatory step at the end of the development to provide guarantees that each of the future results during routine use will be accurate and precise. Conventionally, the performance of the NIR method is evaluated by chemometric parameters.…”