Granule size distributions after twin-screw granulation – Do not forget the feeding systems

Meier, Robin; Thommes, Markus; Rasenack, Norbert; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

doi:10.1016/j.ejpb.2016.05.011

Cited by 44 publications

(19 citation statements)

References 44 publications

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“…The screw diameter was 16 mm and the length (L) of the screws was 41 times the diameter (D). The screw consisted of conveying elements to transport the powder and the granules with minimum shear stress, kneading elements to promote a mixing of powder and liquid and to densify granules and distributive flow elements, to narrow the granule sizes [6,14,15]. The screw was configured as follows: 1 kneading disc ( Powder was fed with a loss-in-weight twin-screw feeder (K-ML-KT 20, K-Tron, Switzerland) into the first zone of the extruder at a set feed-rate of 20 g min -1 .…”

Section: Twin-screw Granulationmentioning

confidence: 99%

Simplified, High Drug‐Loaded Formulations Containing Hydrochlorothiazide for Twin‐Screw Granulation

Meier

Moll

Krumme

et al. 2017

Chemie Ingenieur Technik

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Simplified, high drug loaded formulations for use in twin-screw granulation and tableting were introduced, using the plastically deforming drug ibuprofen. This concept was enlarged by application of hydrochlorothiazide, because opposed deformation behavior was expected to result in different product performances. In most instances the results differed. Critical quality attributes like granule size distribution, disintegration time, and tensile strength of tablets could be met. The study confirms the suitability of simplified formulation with differently behaving drugs for pharmaceutical product design in continuous manufacturing.

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Section: Twin-screw Granulationmentioning

confidence: 99%

Simplified, High Drug‐Loaded Formulations Containing Hydrochlorothiazide for Twin‐Screw Granulation

Meier

Moll

Krumme

et al. 2017

Chemie Ingenieur Technik

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“…For further details of the pump, the reader is referred to previously published studies. 4,14 Liquid feed rate was monitored by a Coriolis mass flow measurement system (Proline Promass 80A; EndressþHauser, Weil am Rhein, Germany). The applied liquid to solid ratios (L/S) are specified in Table 1.…”

Section: Twin Screw Granulationmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] Most of the studies examined process analytical tools for TSG or the influence of process parameters on critical quality attributes (CQAs) of granules or subsequently produced tablets. [8][9][10][11][12][13][14] In these studies, the pharmaceutical formulations were often kept constant, resulting in little data on formulation dependencies of the process. Some studies dealt with formulation changes at constant process parameters and used different batches, polymorphs, or qualities of the same substance, [15][16][17][18] or varied the hydrophobicity of the formulation by the mass ratio of the applied excipients.…”

Section: Introductionmentioning

confidence: 99%

How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant

Meier

Moll

Krumme

et al. 2017

Journal of Pharmaceutical Sciences

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This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule.

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“…3,4 However, in reality the appearance of changes in raw material properties, equipment status with respect to physical wear and varying ambient conditions contribute to disturbances which vary in time and demand for continuous corrective actions during production. 7 Recent studies in the field of continuous drug product manufacturing have therefore investigated the potential to continuously detect undesired powder feed rate deviations and their accompanied disturbances in product uniformity at an early stage using process understanding and advanced monitoring tools. The traditional manufacturing approach which generally adopts automatic regulatory process control in combination with manual supervision, does not compensate in real-time for such critical quality attribute (CQA) variations.…”

Section: Introductionmentioning

confidence: 99%

“…Not only is this necessary to ensure the final drug potency despite process disturbances, but also to ensure the physical characteristics of the intermediate product. 7 Recent studies in the field of continuous drug product manufacturing have therefore investigated the potential to continuously detect undesired powder feed rate deviations and their accompanied disturbances in product uniformity at an early stage using process understanding and advanced monitoring tools. [8][9][10][11] The next step is to use the acquired knowledge and monitoring tools to control the continuous feeding of the raw materials.…”

Section: Introductionmentioning

confidence: 99%

Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

et al. 2018

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Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (%w/w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25%w/w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2500–2514, 2018

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Granule size distributions after twin-screw granulation – Do not forget the feeding systems

Cited by 44 publications

References 44 publications

Simplified, High Drug‐Loaded Formulations Containing Hydrochlorothiazide for Twin‐Screw Granulation

Simplified, High Drug‐Loaded Formulations Containing Hydrochlorothiazide for Twin‐Screw Granulation

How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant

Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

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