Mechanistic approach in powder blending PAT: Bi-layer mixing and asymptotic end point prediction

Šibík, Juraj; Chalus, Pascal; Maurer, Lene; Murthy, Avinash; Krimmer, Siegfried

doi:10.1016/j.powtec.2016.12.038

Cited by 11 publications

(3 citation statements)

References 33 publications

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“…Blending aims to produce a homogeneous mixture of drug and excipient particles that accurately represents the desired ratios of the components. The mixing homogeneity is commonly monitored in batch blending to detect the end point of the mixing (Berntsson et al, 2002;Crouter and Briens, 2019;Pestieau et al, 2014;Sibik et al, 2017). For continuous processes, the mixing homogeneity is assessed of a continuous stream of powder, which enables feedback process control as well as in-process control to divert material to waste.…”

Section: Blend Mixing Homogeneity and Tablet Content Uniformitymentioning

confidence: 99%

Review of real-time release testing of pharmaceutical tablets: State-of-the art, challenges and future perspective

Markl

Warman

Dumarey

et al. 2020

International Journal of Pharmaceutics

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In the last decade significant advances have been made in process analytical technologies and digital manufacturing of pharmaceutical oral solid dosage forms leading to enhanced product knowledge and process understanding. These developments provide an excellent platform for realising real-time release testing (RTRT) to eliminate all, or certain, off-line end product tests assuring that the drug product is of intended quality. This review article presents the state of the art, an RTRT development workflow as well as challenges and opportunities of RTRT in batch and continuous manufacturing of pharmaceutical tablets. Critical quality attributes, regulatory aspects and the scientific basis of enabling technologies and models for RTRT are discussed and a systematic development workflow for the robust design of an RTRT environment is presented. This includes the discussion of key considerations for the identification of the critical quality attributes and points of testing as well as the development of the sampling strategy, a hard and/or soft sensor approach and operational procedures. The final sections present two RTRT use cases in an industrial setting as well as critically discuss challenges and provide a future perspective of RTRT.

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Section: Blend Mixing Homogeneity and Tablet Content Uniformitymentioning

confidence: 99%

Review of real-time release testing of pharmaceutical tablets: State-of-the art, challenges and future perspective

Markl

Warman

Dumarey

et al. 2020

International Journal of Pharmaceutics

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show abstract

“…18,19 Furthermore, while it is known that calibrationbased solutions are widely used for end-point determination, the calibration-free methods have been increasingly utilized to achieve this goal, in which the moving block standard deviation (MBSD) method is able to monitor the process status and determine the end-point depending on the spectral difference. 20,21 Yet, few studies have explored the end-point determination of column chromatographic processes by attempting to apply calibration-based or calibration-free methods.…”

Section: Introductionmentioning

confidence: 99%

Real-time monitoring of the column chromatographic process of Phellodendri Chinensis Cortex part I: end-point determination based on near-infrared spectroscopy combined with machine learning

Cui

et al. 2022

New J. Chem.

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“…Alternatively, a more flexible way that removes some challenges of both qualitative and quantitative methods has become increasingly attractive [27,28]. A typical version of such methods is moving window F test (MW-F test) derived from the Caterpillar algorithm, the main idea of which is to compare the current variation of the process with its recent variation [29,30].…”

Section: Introductionmentioning

confidence: 99%

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

Shi

Zhiqiang

et al. 2019

Processes

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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.

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Mechanistic approach in powder blending PAT: Bi-layer mixing and asymptotic end point prediction

Cited by 11 publications

References 33 publications

Review of real-time release testing of pharmaceutical tablets: State-of-the art, challenges and future perspective

Review of real-time release testing of pharmaceutical tablets: State-of-the art, challenges and future perspective

Real-time monitoring of the column chromatographic process of Phellodendri Chinensis Cortex part I: end-point determination based on near-infrared spectroscopy combined with machine learning

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

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