Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior

Hagrasy, Arwa S. El; Hennenkamp, J.R.; Burke, Matthew D.; Cartwright, J.; Litster, James D.

doi:10.1016/j.powtec.2012.04.035

Cited by 172 publications

(125 citation statements)

References 29 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%

“…Only a limited number of studies on twin screw granulation addressed formulation development while most studies focused on the influence of process parameters on granule quality [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Moreover, most studies used formulations with lactose or microcrystalline cellulose as fillers.…”

Section: Introductionmentioning

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%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…This difference is likely due to the difference in residence time between continuous (5 -20 s) and high shear granulation (tens of minutes) as the substitution degree (and thus hydration rate) only influences granule growth when the contact time between water and polymer is short [24,26,32,36].…”

Section: Influence Of Formulation Variables On Granule Qualitymentioning

confidence: 99%

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Vanhoorne

Janssens

Vercruysse

et al. 2016

International Journal of Pharmaceutics

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HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation.The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24 h with release profiles close to zero-order.The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC.

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“…For wet granulation, a frequently applied intermediate processing step during the production of pharmaceutical solid dosage forms, high shear twin screw granulation, has shown to be a most promising continuous alternative to conventional high shear and fluid bed granulation (Vervaet and Remon, 2005). Nonetheless, twin screw wet granulation is also known for its typical bi-modal granule size distribution (Dhenge et al, 2010;El Hagrasy et al). Granule loads mostly tend to contain either a large amount of fines (<250 µm) or a large amount of oversized granules (>1400 µm).…”

Section: Notementioning

confidence: 99%

Distribution of binder in granules produced by means of twin screw granulation

Fonteyne

Fussell

Vercruysse

et al. 2014

International Journal of Pharmaceutics

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Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior

Cited by 172 publications

References 29 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

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Distribution of binder in granules produced by means of twin screw granulation

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