Comparison between integrated continuous direct compression line and batch processing – The effect of raw material properties

Karttunen, Anssi-Pekka; Wikström, Håkan; Tajarobi, Pirjo; Fransson, Magnus; Sparén, Anders; Marucci, Mariagrazia; Ketolainen, Jarkko; Folestad, Staffan; Korhonen, Ossi; Abrahmsén-Alami, Susanna

doi:10.1016/j.ejps.2019.03.001

Cited by 34 publications

(22 citation statements)

References 41 publications

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“…This provides assurance that it is not just a result of a poorer prediction model. The results are in line with our previous papers showing that the variation in the API content between tablets during steady processing was higher in formulation B than in formulation A (Karttunen et al, 2019b;Lakio et al, 2017).…”

Section: Pulse Disturbance Runssupporting

confidence: 93%

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Robustness of a continuous direct compression line against disturbances in feeding

Karttunen

Poms

Sacher

et al. 2020

International Journal of Pharmaceutics

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Section: Pulse Disturbance Runssupporting

confidence: 93%

“…The formulations in this study were selected from those used in the previous studies in the same line (Karttunen et al, 2019b;Lakio et al, 2017). The materials, their respective grades and formulation compositions are shown in Table 1.…”

Section: Formulationsmentioning

confidence: 99%

Robustness of a continuous direct compression line against disturbances in feeding

Karttunen

Poms

Sacher

et al. 2020

International Journal of Pharmaceutics

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“…It is also important to note that there is not a simple cut-off in performance at three, and that materials close to this FFC are likely to be difficult, regardless of whether they fall over or under the nominal FFC limit of 3. Recent data has suggested that, in some cases, materials with a FFC<3 do not perform in all circumstances in LIW feeder systems 17 . In some cases, for powders with unacceptable flow and performance, it has been necessary to pre-blend drug powders with flow aids to achieve the necessary performance in the continuous system, which adds a batch process (the pre-blending) to the nominally continuous one.…”

Section: Introductionmentioning

confidence: 99%

“…Capturing all of these factors can be difficult, but multivariate and other modelling approaches are used to understand better the factors, and their interrelationships. 17,18 It is recognised that engineering of materials to ensure performance in LIW feeders is a possible, and perhaps necessary, adjunct to the successful use of such manufacturing approaches. 1 The composition (material) and geometry of a feeding system also makes a significant difference to the flow that a material achieves through the system, as can other perturbations such as when the feeding system is topped up 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

et al. 2020

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Purpose: Understanding and predicting the flow of bulk pharmaceutical materials could be key in enabling pharmaceutical manufacturing by continuous direct compression (CDC). This study examines whether, by taking powder and bulk measurements, and using statistical modelling, it would be possible the flow of a range of materials likely to be used in CDC. Methods: More than 100 materials were selected for study, from four pharmaceutical companies. Particle properties were measured by static image analysis, powder surface area and surface energy techniques, and flow by shear cell measurements. The data was then analysed and a range of statistical modelling techniques were used, to build predictive models for flow. Results: Using the results from static image analysis a model could be built which allowed the prediction of likely flow in a shear cell, which can be related to performance in a CDC system. Only a small amount of powder was required for the image analysis. Surface area did not add to the precision of the model, and the available surface energy technique did not correlate with flow. Conclusions: A small sample of powder can be examined by Static image analysis, and this data can be used to give an early read on likely flow of a material in a CDC system or other pharmaceutical process, allowing early intervention (if necessary) to improve the characteristics of a material, early in development.

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“…Continuous mixing has been shown to be capable to produce more homogenous mixtures as compared to batch mixing [8,[19][20][21][22], thus, a continuous direct compression (CDC) set-up, where the amount of material that is being processed at a certain timepoint could be minimized by small mass hold-ups, is a promising method for low-dose manufacturing. Recently, encouraging results were obtained by Karttunen et al (2019) when they compared a CDC process to traditional batch manufacturing [23]. The possibility of equipping the manufacturing line with suitable process analytical technology (PAT) tools, enabling the monitoring of API concentration during processing (and capability to reveal if problems are about to occur), makes it even more attractive [24].…”

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confidence: 99%

The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process

et al. 2020

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Segregation is a common problem in batch-based direct compression (BDC) processes, especially with low-dose tablet products, as is the preparation of a homogenous mixture. The scope of the current work was to explore if a continuous direct compression (CDC) process could serve as a solution for these challenges. Furthermore, the principle of a platform formulation was demonstrated for low dose tablets. The combination of filler excipients and the API in the formulation used was suitable for direct compression, but also prone to induce segregation in BDC process. The CDC process was found to be very promising; it was shown that tablets with the desired quality parameters could be manufactured successfully with both of the APIs studied. Powder analysis indicated that the APIs display some fundamental differences in their physical properties, which was also reflected in powder mixture properties and, hence, eventually in processing. However, process parameters, especially mixer impeller speed, were not found to have any significant influence on end product quality. The study suggests that a CDC process can be a viable solution to resolve the challenges described. Moreover, manufacturing by using a universal platform formulation seems to be a feasible way for producing low-dose tablets.

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Comparison between integrated continuous direct compression line and batch processing – The effect of raw material properties

Cited by 34 publications

References 41 publications

Robustness of a continuous direct compression line against disturbances in feeding

Robustness of a continuous direct compression line against disturbances in feeding

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process

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