Real-time feedback control of twin-screw wet granulation based on image analysis

Madarász, Lajos; Nagy, Zsombor Kristóf; Hoffer, I; Szabó, Barna; Csontos, István; Pataki, Hajnalka; Démuth, Balázs; Szabó, Bence; Csorba, Kristóf; Marosi, György

doi:10.1016/j.ijpharm.2018.06.003

Cited by 36 publications

(18 citation statements)

References 21 publications

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“…Therefore, the application of the latter two pumps is recommended when homogeneity of the liquid (and possibly, the dissolved drug) is of great importance. The inconsistent feeding of the granulating liquid may lead to more disadvantageous PSDs [12] (besides the inhomogeneous drug distribution) especially if the granulating agent is dissolved in it.…”

Section: Pump Characteristics -The Dosing Profilesmentioning

confidence: 99%

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Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Démuth

Fülöp

Kovacs

et al. 2020

Period. Polytech. Chem. Eng.

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Homogeneous ultralow-dose (30 mg) tablets were prepared from perfectly free-flowing granules manufactured by continuous Twin-Screw Wet Granulation. The gravimetrically fed mixture of lactose and potato starch of low particle size was successfully agglomerated and the size enlargement technology proved to be very robust. Since the incorporated drug was dissolved in ethanol-based granulation liquid, the resulting homogeneity largely depended on the dosing of the applied liquid administering units.A peristaltic pump generated higher deviation of the drug content in tablets (Relative Standard Deviation (RSD): 7.7 %) compared to a syringe pump (RSD: 2.3 %) or a piston pump (RSD: 4.6 %). This is due to the pulsation of the liquid flow generated by the peristaltic pump according to the real-time measured mass of the fed liquid. A good correlation was found between the RSD of the liquid mass flow (calculated from the recorded masses) and the RSD of the drug content. Based on the results, the goodness of Content Uniformity, as the most relevant critical quality attribute of low-dose products, was determined by the characteristics of the applied dosing units. The feeding characteristic of the different pumps could be easily measured by the introduced balance-based method and therefore, the applicability of the pumps could be evaluated.

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Section: Pump Characteristics -The Dosing Profilesmentioning

confidence: 99%

“…Since continuous technologies are heavily promoted by the authorities [7,8], intense R&D efforts are going into their possible industrial applications [9,10]. Numerous papers have been published based on the research conducted on Twin-Screw Granulators [11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Démuth

Fülöp

Kovacs

et al. 2020

Period. Polytech. Chem. Eng.

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“…Continuous (bio)pharmaceutical technology became the main subject of our research work in this field. Melt and wet extrusion of a several model drugs [45,46] helped to develop a unique infrastructure suitable for forming drug-containing fine foamed structures. Supercritical pharmaceutical extrusion technology [47] proved to be feasible both for forming floating tablet of sustained release and fast-release milled foams, containing tolperisone and spironolactone respectively, according to Figs.…”

Section: Technologies Of Innovative Pharmaceuticalsmentioning

confidence: 99%

Pharmaceutical and Macromolecular Technologies in the Spirit of Industry 4.0

Marosi

Hirsch

Bocz

et al. 2018

Period. Polytech. Chem. Eng.

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Well designed (multilayer, adaptive, reactive) interphases, being a key element of multicomponent structures, could be tailored to different requirements through controlled technologies. This is the link connecting various green, safe, healthy materials and innovative pharmaceuticals. Upgraded recycling could be performed by interfacial consolidation of self-reinforced composites, the flame retardancy of which is feasible with surprisingly low amount of flame retardant. Examples are shown how the reinforced and foamed forms of thermosetting and thermoplastic biopolymers can play a significant role (after flame retardant modification) in the development of airplanes and electric cars. Biopolymer nanofibres, such as polycaprolactone and polyhydroxybutyrate, could be formed with increased productivity for various medical uses. Raman-based control of the units of integrated continuous technologies has been elaborated including controlled formation of crystals with polymer interlayer for direct tableting.

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“…Therefore, development of in-line or on-line particle size measurements are of interest. Numerous techniques (e.g., dynamic image analysis (DIA), laser diffraction, focused beam reflectance measurement, spatial filtering technique) have been reported to be implemented in discontinuous or continuous processing of pharmaceuticals [25][26][27][28][29][30]. GSD monitoring for RCDG is impeded by the high throughput of the process, resulting in a high number of granules, and the broad size distribution that typically results from dry granulation.…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of an In-line and On-line Monitoring System for Granule Size Distributions in Continuous Roll Compaction/Dry Granulation Based on Laser Diffraction

2020

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Purpose Roll compaction/dry granulation is established in manufacturing of solid oral dosage forms and, within the context of continuous manufacturing, it has sparked interest as material is fed, processed, and ejected continuously while also providing large possible throughputs. However, this amount of material has to be adequately controlled in real time to assure quality. Methods This research aimed at monitoring the critical quality attribute granule size distribution in continuous roll compaction/ dry granulation (QbCon®; L.B. Bohle, Ennigerloh, Germany) using in-line and on-line laser diffraction. The influence of varying process parameters and excipient formulations was studied and evaluated with the prospect of using this technique to develop control loops. For this purpose, residence time parameters were assessed. In-and on-line data was compared with off-line laser diffraction and dynamic image analysis data. Results The system successfully monitored the granule size distribution in a variety of process parameters and throughputs (up to 27.5 kg/h). It was sensitive to changes in process parameters and changes in material blends, which could pose a potential threat to the final drug products' quality. Average event propagation time from the compaction zone to the laser diffraction system of 17.7 s demonstrates the systems' fast reaction time. Conclusion Results highlight laser diffraction as a valuable method of in-and on-line size determination and allow for the development of a control strategy using this principle.

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Real-time feedback control of twin-screw wet granulation based on image analysis

Cited by 36 publications

References 21 publications

Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

Pharmaceutical and Macromolecular Technologies in the Spirit of Industry 4.0

Development and Evaluation of an In-line and On-line Monitoring System for Granule Size Distributions in Continuous Roll Compaction/Dry Granulation Based on Laser Diffraction

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