Analytical Method Quality by Design for an On-Line Near-Infrared Method to Monitor Blend Potency and Uniformity

Corredor, Claudia C.; Lozano, Ruben; Bu, Xin; McCann, Ryan; Dougherty, Jeffrey; Stevens, Tim; Both, Douglas; Shah, Pankaj A.

doi:10.1007/s12247-014-9205-2

Cited by 29 publications

(10 citation statements)

References 28 publications

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“…Much of the current literature on the manufacturing of solid dosage forms pays particular attention to techniques for in-line monitoring of the blend uniformity, with near-infrared spectroscopy (NIRS) being the most widely-employed process analyzer [11][12][13][14][15][16][17]. Other non-destructive techniques, such as Raman spectroscopy [18][19][20], light induced fluorescence [21] and chemical imaging [22][23][24][25], are used for on-and in-line measuring of the blend uniformity [26].…”

Section: Introductionmentioning

confidence: 99%

Measuring bulk density variations in a moving powder bed via terahertz in-line sensing

Stranzinger

Faulhammer

et al. 2019

Powder Technology

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Monitoring the relative density of static or moving powder inside a process line is essential for manufacturing high-quality products. The aim of this study was to predict density variations in a moving powder bed using terahertz reflection technology. We systematically investigated three grades (varying true density and particle size) of two materials: lactose and silicified microcrystalline cellulose (SMCC). These six powders specifically differ in their compressibility, which can be applied to assess the sensitivity and applicability of our method. The powders were filled into a round container, and terahertz reflection measurements were acquired continuously during the container's rotation. The setup allowed to adjust the relative density by compacting the powders into specific powder bed heights. Each powder was compacted to various relative densities (compression pressures up to 100 kPa). We calculated the surface refractive index based on the in-line terahertz measurements acquired during rotation, which has a linear dependence on the relative density of the powder. This was confirmed by correlating the refractive index values with the theoretical relative densities based on the bulk and true densities of the powder. The coefficient of determination (2) was larger than 0.962 (Lactohale 100) for all six powders, with the highest coefficients for Lactohale 220 (2 = 0.996) and SMCC 50 LD (2 = 0.995). The results suggest that the proposed method can resolve relative densities averaged across the powder bed that are as small as 0.3% (Lactohale 100). The high acquisition rate of the terahertz system (15 Hz) made it possible to determine the powder density in 230 positions uniformly distributed throughout the container, facilitating the investigation of the relative density uniformity in the container as a function of the powder bed height. It was observed that SMCC powders undergo a smaller change in the relative density variations upon compaction than the lactose powders. Moreover, the relative density maps clearly indicate local density differences in the powder bed for all powders. The relative density variations (in the horizontal direction) that were introduced by packing of the container prevailed throughout the compaction process for all samples with the exception of Lactohale 220. The presented approach allows a precise resolution of the spatial distribution of relative density, which facilitates an in-depth analysis of powder behavior upon compaction.

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Section: Introductionmentioning

confidence: 99%

Measuring bulk density variations in a moving powder bed via terahertz in-line sensing

Stranzinger

Faulhammer

et al. 2019

Powder Technology

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“…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.…”

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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“…High-performance liquid chromatography has been widely used as a standard off-line reference method for homogeneity analysis [44,45]. Non-invasive techniques such as near-infrared (NIR) spectroscopy [46][47][48][49][50][51][52] and chemical imaging [53][54][55], Raman spectroscopy [56][57][58], and lightinduced fluorescence [31,59] are also widely used for on-line or in-line measurement of blend uniformity. Of the large number of publications describing such techniques for blend uniformity Page 9 of 43 A c c e p t e d M a n u s c r i p t 8 analysis, however, few have noted the impact of effective sample volume on homogeneity analysis.…”

Section: Introductionmentioning

confidence: 99%

Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders

Wang

Barona

Oladepo

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

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Analytical Method Quality by Design for an On-Line Near-Infrared Method to Monitor Blend Potency and Uniformity

Cited by 29 publications

References 28 publications

Measuring bulk density variations in a moving powder bed via terahertz in-line sensing

Measuring bulk density variations in a moving powder bed via terahertz in-line sensing

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

Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders

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