The Effect of Binder Types on the Breakage and Drying Behavior of Granules in a Semi-Continuous Fluid Bed Dryer after Twin Screw Wet Granulation

2022 ◽  
pp. 121449
Author(s):  
L. Vandevivere ◽  
P. Denduyver ◽  
C. Portier ◽  
O. Häusler ◽  
T. De Beer ◽  
...  
Keyword(s):  
Wet Granulation ◽  
Fluid Bed ◽  
Twin Screw ◽  
Drying Behavior

scholarly journals The Influence of Equipment Design and Process Parameters on Granule Breakage in a Semi-Continuous Fluid Bed Dryer after Continuous Twin-Screw Wet Granulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 293
Author(s):  
Alexander Ryckaert ◽  
Michael Ghijs ◽  
Christoph Portier ◽  
Dejan Djuric ◽  
Adrian Funke ◽  
...  
Keyword(s):  
Process Development ◽  
Wet Granulation ◽  
Major Goal ◽  
Drying Time ◽  
Process Step ◽  
Manufacturing Line ◽  
Fluid Bed ◽  
Twin Screw ◽  
Filling Phase ◽  
Twin Screw Granulation

The drying unit of a continuous from-powder-to-tablet manufacturing line based on twin-screw granulation (TSG) is a crucial intermediate process step to achieve the desired tablet quality. Understanding the size reduction of pharmaceutical granules before, during, and after the fluid bed drying process is, however, still lacking. A first major goal was to investigate the breakage and attrition phenomena during transport of wet and dry granules, the filling phase, and drying phase on a ConsiGma-25 system (C25). Pneumatic transport of the wet granules after TSG towards the dryer induced extensive breakage, whereas the turbulent filling and drying phase of the drying cells caused rather moderate breakage and attrition. Subsequently, the dry transfer line was responsible for additional extensive breakage and attrition. The second major goal was to compare the influence of drying air temperature and drying time on granule size and moisture content for granules processed with a commercial-scale ConsiGma-25 system and with the R&D-scale ConsiGma-1 (C1) system. Generally, the granule quality obtained after drying with C1 was not predictive for the C25, making it challenging during process development with the C1 to obtain representative granules for the C25.

scholarly journals Evaluation of Binders in Twin-Screw Wet Granulation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 241
Author(s):  
Claudia Köster ◽  
Sebastian Pohl ◽  
Peter Kleinebudde
Keyword(s):  
Molecular Weight ◽  
Tensile Strength ◽  
Wet Granulation ◽  
Compression Pressure ◽  
Demineralized Water ◽  
Twin Screw

The binders povidone (Kollidon 30), copovidone (Kollidon VA64), hypromellose (Pharmacoat 606), and three types of hyprolose (HPC SSL-SFP, HPC SSL, and HPC SL-FP) were evaluated regarding their suitability in twin-screw wet granulation. Six mixtures of lactose and binder as well as lactose without binder were twin-screw granulated with demineralized water at different barrel fill levels and subsequently tableted. A screening run with HPC SSL determined the amount of water as an influential parameter for oversized agglomerates. Subsequent examination of different binders, especially Kollidon 30 and Kollidon VA64 resulted in large granules. All binders, except Pharmacoat 606, led to a reduction of fines compared to granulation without a binder. The molecular weight of applied hyproloses did not appear as influential. Tableting required an upstream sieving step to remove overlarge granules. Tableting was possible for all formulations at sufficient compression pressure. Most binders resulted in comparable tensile strengths, while Pharmacoat 606 led to lower and lactose without a binder to the lowest tensile strength. Tablets without a binder disintegrated easily, whereas binder containing tablets of sufficient tensile strength often nearly failed or failed the disintegration test. Especially tablets containing Pharmacoat 606 and HPC SL-FP disintegrated too slowly.

scholarly journals Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 210
Author(s):  
Lise Vandevivere ◽  
Maxine Vangampelaere ◽  
Christoph Portier ◽  
Cedrine de Backere ◽  
Olaf Häusler ◽  
...  
Keyword(s):  
Dissolution Kinetics ◽  
Wet Granulation ◽  
Continuous Manufacturing ◽  
Formulation Development ◽  
Granulation Process ◽  
Low Viscosity ◽  
Twin Screw ◽  
Poorly Soluble ◽  
Selection For ◽  
The Impact

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

A combined experimental and computational study of wet granulation in a Wurster fluid bed granulator

2009 ◽  
Vol 189 (2) ◽  
pp. 190-201 ◽  
Author(s):  
P. Rajniak ◽  
F. Stepanek ◽  
K. Dhanasekharan ◽  
R. Fan ◽  
C. Mancinelli ◽  
...  
Keyword(s):  
Computational Study ◽  
Wet Granulation ◽  
Fluid Bed

scholarly journals End-Point Prediction of Granule Moisture in a ConsiGmaTM-25 Segmented Fluid Bed Dryer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 452
Author(s):  
Jakob Rehrl ◽  
Stephan Sacher ◽  
Martin Horn ◽  
Johannes Khinast
Keyword(s):  
Process Model ◽  
Operating Conditions ◽  
Pharmaceutical Manufacturing ◽  
Wet Granulation ◽  
Drying Time ◽  
Proposed Model ◽  
Fluid Bed ◽  
Continuous Dryer ◽  
Process Measurements ◽  
Validation Experiments

Continuously operated pharmaceutical manufacturing lines often consist of a wet granulation unit operation, followed by a (semi-) continuous dryer. The operating conditions of the dryer are crucial for obtaining a desired final granule moisture. Commercially available dryers lack of a thorough online measurement of granule moisture during the drying process. However, this information could improve the operation of the equipment considerably, yielding a granule moisture close to the desired value (e.g., by drying time and process parameter adjustments in real-time). The paper at hand proposes a process model, which can be parameterized from a very limited number of experiments and then be used as a so-called soft sensor for predicting granule moisture. It utilizes available process measurements for the estimation of the granule moisture. The development of the model as well as parameter identification and validation experiments are provided. The proposed model paves the way for the application of sophisticated observer concepts. Possible future activities on that topic are outlined in the paper.

Native starch as in situ binder for continuous twin screw wet granulation

2019 ◽  
Vol 571 ◽  
pp. 118760 ◽  
Author(s):  
Lise Vandevivere ◽  
Christoph Portier ◽  
Valérie Vanhoorne ◽  
Olaf Häusler ◽  
Denis Simon ◽  
...  
Keyword(s):  
Wet Granulation ◽  
Native Starch ◽  
Twin Screw

scholarly journals Assessment of Abrasion-Induced Visual Defects in Twin Screw Wet Granulation Using Wall Friction Measurements

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Judith Menth ◽  
Martin Maus ◽  
Karl G. Wagner
Keyword(s):  
Friction Angle ◽  
Wall Friction ◽  
Wall Material ◽  
Process Window ◽  
Wet Granulation ◽  
Visual Defect ◽  
Defect Rate ◽  
Starting Point ◽  
Twin Screw ◽  
Friction Measurements

AbstractStarting point of the presented study were abrasion effects occurring during a twin screw wet granulation (TSG) process of a new chemical entity (NCE) formulation, resulting in gray spots on the final tablets. Several actions and systematic changes of equipment and process parameter settings of TSG process were conducted which reduced the visual defect rate of the tablets, i.e., gray spots on the surface, below the specification limit. To understand the rationale and mechanism behind these improvements, correlations of defect rates and wall friction measurements using a Schulze ring shear tester were evaluated. To check the suitability of the method, a broad range of wall materials as well as powder formulations at various moisture levels were investigated with regard to their wall friction angle. As differences in wall friction angle could be detected, further experiments were conducted using wall material samples made out of different screw materials for TSG. Evaluation of these screw wall material samples gave first hints, which screw materials should be preferred in regard of friction for TSG process. In the finally presented case study, wall friction measurements were performed using the above mentioned NCE formulation with known abrasion issues at TSG processing. The results confirmed that changes which led to a reduced visual defect rate of tablets correlated with a decreased wall friction angle. The results suggest wall friction measurements as a potent tool for equipment selection and establishment of a suitable process window prior to conducting TSG experiments. Graphical abstract

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