Continuous quantitative monitoring of powder mixing dynamics by near-infrared spectroscopy

Koller, Daniel; Posch, Andreas E.; Hörl, Gudrun; Voura, Christine; Radl, Stefan; Urbanetz, Nora Anne; Fraser, Simon D.; Tritthart, Walter; Reiter, Franz; Schlingmann, M.; Khinast, Johannes G.

doi:10.1016/j.powtec.2010.08.070

Cited by 64 publications

(39 citation statements)

References 41 publications

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“…This is further evidence of the difficulty of analyzing blends. A careful review of previous publications revealed that very few studies have compared real-time NIR measurements and off-line measurements [6,[19][20][21]. This comparison is not easy since the NIR method is providing the concentration of a sample volume that is approximately 300 mg while the sample analyzed by UV is about 3 g. The authors recognize that additional experimental work is required to evaluate the difference between UV and NIR results.…”

Section: Real-time Monitoring Of Continuous Blending Processmentioning

confidence: 99%

Near Infrared Method Development for a Continuous Manufacturing Blending Process

et al. 2014

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Purpose This study describes the validation of a near infrared spectroscopic method for monitoring a continuous manufacturing system. The achievement of this goal requires determining the near infrared (NIR) method's accuracy, precision, obtaining an estimate of the sample volume analyzed, and the frequency with which measurements should be obtained. Methods Five calibration blends were prepared spanning a concentration range from 7 to 13 % w/w ibuprofen to prepare a partial least squares (PLS) calibration model for a five component formulation. NIR spectra were obtained after powders passed through feeders and a custom-made tumble mixer. The calibration model's precision and accuracy were determined with the prediction of three validation blends. Results NIR concentration predictions obtained from spectra collected during the validation runs showed relative standard errors of predictions of 2.8 % at target concentration with standard deviations NMT 0.2 % w/w. At certain time points, blend samples coming out of the blender were collected for UV analysis. Results from the NIR and UV analysis were comparable with the largest difference being 0.36 % w/w between the methods. A continuous blending process was monitored for 3 min after steady-state conditions were achieved. All individual predictions were within 3 standard deviations of the average reference value. The standard deviation for the NIR concentration predictions was 0.49 % w/w. Conclusion The use of the standard normal variate (SNV) transform significantly reduced the effect of differences in powder flow on the NIR predictions. The use of variograms provided valuable insight into the frequency of measurements needed for the continuous manufacturing system. Additional research is needed to investigate the differences observed in the NIR and UV results for the continuous manufacturing run.

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Section: Real-time Monitoring Of Continuous Blending Processmentioning

confidence: 99%

Near Infrared Method Development for a Continuous Manufacturing Blending Process

et al. 2014

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“…The previously mentioned powders tend to segregate, as described in the literature (25). Typically, ASA particles rise to the top due to their larger size.…”

Section: Calibrationmentioning

confidence: 80%

“…Overcoming the problems associated with differences between calibration and measurement has been discussed in the literature (20,21). Moreover, the dynamics of blending processes have been studied theoretically as well (22,23) and experimentally using model substances (24) and pharmaceutical powders (25). However, using one probe in the same position usually does not provide a reliable assessment of the blending process (21,26).…”

Section: Introductionmentioning

confidence: 99%

Monitoring Blending of Pharmaceutical Powders with Multipoint NIR Spectroscopy

et al. 2012

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Abstract. Blending of powders is a crucial step in the production of pharmaceutical solid dosage forms. The active pharmaceutical ingredient (API) is often a powder that is blended with other powders (excipients) in order to produce tablets. The blending efficiency is influenced by several external factors, such as the desired degree of homogeneity and the required blending time, which mainly depend on the properties of the blended materials and on the geometry of the blender. This experimental study investigates the mixing behavior of acetyl salicylic acid as an API and α-lactose monohydrate as an excipient for different filling orders and filling levels in a blender. A multiple near-infrared probe setup on a laboratoryscale blender is used to observe the powder composition quasi-simultaneously and in-line in up to six different positions of the blender. Partial least squares regression modeling was used for a quantitative analysis of the powder compositions in the different measurement positions. The end point for the investigated mixtures and measurement positions was determined via moving block standard deviation. Observing blending in different positions helped to detect good and poor mixing positions inside the blender that are affected by convective and diffusive mixing.

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“…Powder properties, particularly cohesiveness and flow properties, can also affect mixing performance [35,[37][38][39]. As is the case for hoppers, if components in the blend have very different properties (particle size and density) segregation may occur [40]. Several metrics can be used to monitor mixing efficiency.…”

Section: Continuous Mixersmentioning

confidence: 99%

Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

2013

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Abstract:The objective of this work is to present a review of computational tools and models for pharmaceutical processes, specifically those for the continuous manufacture of solid dosage forms. Relevant mathematical methods and simulation techniques are discussed, as is the development of process models for solids-handling unit operations. Continuous processing is of particular interest in the current study because it has the potential to improve the efficiency and robustness of pharmaceutical manufacturing processes.

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Continuous quantitative monitoring of powder mixing dynamics by near-infrared spectroscopy

Cited by 64 publications

References 41 publications

Near Infrared Method Development for a Continuous Manufacturing Blending Process

Near Infrared Method Development for a Continuous Manufacturing Blending Process

Monitoring Blending of Pharmaceutical Powders with Multipoint NIR Spectroscopy

Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms

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