Transfer from High‐Shear Batch to Continuous Twin Screw Wet Granulation: A Case Study in Understanding the Relationship Between Process Parameters and Product Quality Attributes

Beer, Paul D.; Wilson, David A.; Huang, Zhaohui; Matas, Marcel de

doi:10.1002/jps.24078

Cited by 36 publications

(12 citation statements)

References 20 publications

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“…The influence of viscosity and substitution degree of HPMC on the drug release rate after direct compression and batch granulation was already extensively studied [4,9,12]. However, a comparative study between twin screw granulation and high shear granulation demonstrated that granules produced by twin screw granulation were denser and that the drug release rate from tablets derived from these dense granules was slower [34]. Therefore the influence of viscosity and substitution degree of HPMC on drug release was investigated after twin screw granulation in the current study.…”

Section: Influence Of the Formulation Variables On Tablet 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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Section: Influence Of the Formulation Variables On Tablet 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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“…Extensive efforts have been made in the last decades to gain fundamental understanding of the wet granulation process in the batch granulators with focus on granule size distribution especially for pharmaceutical applications; yet, little attention has been paid to the continuous process specially the internal structure of granules [2]. It is thus necessary to look more into continuous process simply because it has a significant potential to overcome the drawbacks associated with batch process and offers numerous advantages [3][4][5]. DEM modelling as a robust numerical method can help the manufacturers to have a better understanding of the mechanisms behind the continuous granulation.…”

Section: Introductionmentioning

confidence: 99%

An investigation on process of seeded granulation in a continuous drum granulator using DEM

Behjani

Rahmanian

Ghani

et al. 2017

Advanced Powder Technology

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Numerical simulation of wet granulation in a continuous granulator is carried out using Discrete Element Method (DEM) to discover the possibility of formation of seeded granules in a continuous process with the aim of reducing number of experimental trials and means of process control. Simple and scooped drum granulators are utilized to attain homogenous seeded granules in which the effects of drum rotational speed, particles surface energy, and particles size ratio are investigated. To reduce the simulation time a scale-up scheme is designed in which a dimensionless number (Cohesion number) is defined based on the work of cohesion and gravitational potential energy of the particles. Also a mathematical/numerical method along with a MATLAB code is developed by which the percentage of surface coverage of each granule is predicted precisely. The results show that use of continuous granulator is promising provided that a high level of shear is considered in the granulator design, i.e. using baffles inside drum granulators is essential for producing seeded granules. It is observed that the optimum surface energy for seeded granulation in scooped granulator (used in this study) with rotational speed of 50 rpm is 3 J/m 2 , which is close to the value predicted by the concept of Cohesion number.It is also shown that increasing the seed/fine size ratio enhances the seeded granulation both quantitatively (60% increase in seeds surface coverage) and qualitatively (more homogeneous granules).

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“…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%

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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Transfer from High‐Shear Batch to Continuous Twin Screw Wet Granulation: A Case Study in Understanding the Relationship Between Process Parameters and Product Quality Attributes

Cited by 36 publications

References 20 publications

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

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

An investigation on process of seeded granulation in a continuous drum granulator using DEM

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

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