Methodology for a Variable Rate Control Strategy Development in Continuous Manufacturing Applied to Twin-screw Wet-Granulation and Continuous Fluid-bed Drying

2018 ◽  
Vol 13 (3) ◽  
pp. 247-260 ◽  
Author(s):  
Victoria Pauli ◽  
Frantz Elbaz ◽  
Peter Kleinebudde ◽  
Markus Krumme
Keyword(s):  
Control Strategy ◽  
Rate Control ◽  
Strategy Development ◽  
Wet Granulation ◽  
Variable Rate ◽  
Continuous Manufacturing ◽  
Fluid Bed ◽  
Twin Screw

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 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.

scholarly journals Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

2020 ◽  
Vol 64 (4) ◽  
pp. 391-400 ◽  
Author(s):  
Balázs Démuth ◽  
Gergő Fülöp ◽  
Márk Kovács ◽  
Lajos Madarász ◽  
Máté Ficzere ◽  
...  
Keyword(s):  
Potato Starch ◽  
Wet Granulation ◽  
Content Uniformity ◽  
Peristaltic Pump ◽  
Continuous Manufacturing ◽  
Ultralow Dose ◽  
Drug Content ◽  
Relative Standard ◽  
Twin Screw ◽  
Measured Mass

Homogeneous ultralow-dose (30 mg) tablets were prepared from perfectly free-flowing granules manufactured by continuous Twin-Screw Wet Granulation. The gravimetrically fed mixture of lactose and potato starch of low particle size was successfully agglomerated and the size enlargement technology proved to be very robust. Since the incorporated drug was dissolved in ethanol-based granulation liquid, the resulting homogeneity largely depended on the dosing of the applied liquid administering units.A peristaltic pump generated higher deviation of the drug content in tablets (Relative Standard Deviation (RSD): 7.7 %) compared to a syringe pump (RSD: 2.3 %) or a piston pump (RSD: 4.6 %). This is due to the pulsation of the liquid flow generated by the peristaltic pump according to the real-time measured mass of the fed liquid. A good correlation was found between the RSD of the liquid mass flow (calculated from the recorded masses) and the RSD of the drug content. Based on the results, the goodness of Content Uniformity, as the most relevant critical quality attribute of low-dose products, was determined by the characteristics of the applied dosing units. The feeding characteristic of the different pumps could be easily measured by the introduced balance-based method and therefore, the applicability of the pumps could be evaluated.

Continuous Twin Screw Wet Granulation and Drying—Control Strategy for Drug Product Manufacturing

2019 ◽  
Vol 108 (11) ◽  
pp. 3502-3514 ◽  
Author(s):  
Gabriella Dahlgren ◽  
Pirjo Tajarobi ◽  
Eric Simone ◽  
Brendon Ricart ◽  
Jason Melnick ◽  
...  
Keyword(s):  
Control Strategy ◽  
Drug Product ◽  
Wet Granulation ◽  
Twin Screw ◽  
Product Manufacturing

Simplified end-to-end continuous manufacturing by feeding API suspensions in twin-screw wet granulation

2018 ◽  
Vol 133 ◽  
pp. 224-231 ◽  
Author(s):  
Adrian Schmidt ◽  
Hans de Waard ◽  
Klaus-Peter Moll ◽  
Peter Kleinebudde ◽  
Markus Krumme
Keyword(s):  
Wet Granulation ◽  
Continuous Manufacturing ◽  
Twin Screw ◽  
End To End

scholarly journals Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 668
Author(s):  
Christoph Portier ◽  
Chris Vervaet ◽  
Valérie Vanhoorne
Keyword(s):  
Recent Progress ◽  
Research Output ◽  
Raw Material ◽  
Wet Granulation ◽  
Special Focus ◽  
Continuous Manufacturing ◽  
Batch Mode ◽  
General Validity ◽  
Twin Screw ◽  
Manufacturing Technologies

Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in batch mode such as high shear granulation and fluid bed granulation, several equipment manufacturers have designed their own manufacturing setup. This has led to a steep increase in the research output in this field. However, most studies still focused on a single (often placebo) formulation, hence making it difficult to assess the general validity of the obtained results. Therefore, current review provides an overview of recent progress in the field of continuous twin screw wet granulation, with special focus on the importance of the formulation aspect and raw material properties. It gives practical guidance for novel and more experienced users of this technique and highlights some of the unmet needs that require further research.

Dry chip feedrate control using online chip moisture

TAPPI Journal ◽  
2018 ◽  
Vol 17 (05) ◽  
pp. 295-305
Author(s):  
Wesley Gilbert ◽  
Ivan Trush ◽  
Bruce Allison ◽  
Randy Reimer ◽  
Howard Mason
Keyword(s):  
Production Rate ◽  
Control Strategy ◽  
Rate Control ◽  
Near Infrared ◽  
Dry Mass ◽  
The Other ◽  
Process Variability ◽  
Moisture Sensor ◽  
Feedback Control Strategy ◽  
And Control

Normal practice in continuous digester operation is to set the production rate through the chip meter speed. This speed is seldom, if ever, adjusted except to change production, and most of the other digester inputs are ratioed to it. The inherent assumption is that constant chip meter speed equates to constant dry mass flow of chips. This is seldom, if ever, true. As a result, the actual production rate, effective alkali (EA)-to-wood and liquor-to-wood ratios may vary substantially from assumed values. This increases process variability and decreases profits. In this report, a new continuous digester production rate control strategy is developed that addresses this shortcoming. A new noncontacting near infrared–based chip moisture sensor is combined with the existing weightometer signal to estimate the actual dry chip mass feedrate entering the digester. The estimated feedrate is then used to implement a novel feedback control strategy that adjusts the chip meter speed to maintain the dry chip feedrate at the target value. The report details the results of applying the new measurements and control strategy to a dual vessel continuous digester.

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