Mixing and transport during pharmaceutical twin-screw wet granulation: Experimental analysis via chemical imaging

Kumar, Ashish; Vercruysse, Jurgen; Toiviainen, Maunu; Panouillot, Pierre-Emmanuel; Juuti, Mikko; Vanhoorne, Valérie; Remon, Jean Paul; Gernaey, Krist V.; Beer, Thomas De; Nopens, Ingmar

doi:10.1016/j.ejpb.2014.04.004

Cited by 98 publications

(72 citation statements)

References 14 publications

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“…The solubility and the solubility rate of the formulation could be determining factors for the influence of screw speed on granule size. Pure mannitol was used as excipient in current study and has a higher solubility and solubility rate constant than most other commonly used excipients for twin screw granulation (lactose, MCC, active drug substances…) [1,7,8,10,12,13,17,19,20,26,27,39,40]. Whereas higher compressive forces at low screw speed generally favor granule growth with less soluble excipients, granulation of mannitol could be driven by its high and fast solubility, rather than by compressive forces.…”

Section: Size Analysismentioning

confidence: 99%

“…In addition, it was investigated if the polymorphic transition from δ-to β-mannitol, which has only been reported during batch high shear granulation, also occurred during twin screw granulation and whether this transition depended on process parameters as the residence time as well as the liquid content during twin-screw granulation are considerably lower compared to batch granulation processes [6,14,17,19,26,27,28,29].…”

Section: Introductionmentioning

confidence: 99%

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Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Vanhoorne

Bekaert

Peeters

et al. 2016

International Journal of Pharmaceutics

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To refer to or to cite this work, please use the citation to the published version:Vanhoorne V., Bekaert B., Peeters E., De Beer T., Remon J.P., Vervaet C. (2016) Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation. International Journal of Pharmaceutics 506 13-24 DOI: 10.1016/j.ijpharm.2016.04.025 AbstractIn most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness.Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400 -900 rpm), granulation temperature (25 -40 °C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma TM -25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ-to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, lesssoluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different.

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Section: Size Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Vanhoorne

Bekaert

Peeters

et al. 2016

International Journal of Pharmaceutics

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show abstract

“…Changes in screw geometry and operating parameters influence both the mean residence time ( t) and the width of the RTD given by the mean centered variance ðr 2 tm Þ (Kumar et al, 2014b). While the radial mixing by the kneading blocks inside the TSG is related to http://dx.doi.org/10.1016/j.ejps.2015.02.004 0928-0987/Ó 2015 Elsevier B.V. All rights reserved.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, only distributions of passage time rather than a true RTD can be measured using PEPT (Bakalis et al, 2004). Kumar et al (2014b) applied near infrared chemical imaging (NIR-CI) to measure the RTD to conclude that the extent of axial mixing is significantly influenced by the screw configuration and barrel filling degree. The adequateness of the NIR-CI as an analytical tool for the visualization of the process in a TSG requiring fast measurements was established in an earlier study by Vercruysse et al (2013).…”

Section: Introductionmentioning

confidence: 99%

“…Narrow RTDs lead to a uniform product and are generally considered to be favourable. However, axial mixing in addition to the radial mixing is equally required in the TSG to avoid the effect of any inhomogeneities (such as the ones caused by non-optimal performance of the pre-blender and periodicity of the feeders and pumps) at the inlet on the produced granules (Kumar et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

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Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation

Kumar

Vercruysse

Vanhoorne

et al. 2015

European Journal of Pharmaceutical Sciences

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Twin‐screw Granulation Process Development: Present Approaches, Understanding and Needs

Kumar

Gernaey

Beer

2017

Continuous Manufacturing of Pharmaceuticals

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Mixing and transport during pharmaceutical twin-screw wet granulation: Experimental analysis via chemical imaging

Cited by 98 publications

References 14 publications

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation

Twin‐screw Granulation Process Development: Present Approaches, Understanding and Needs

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