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.

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.

Managing API raw material variability during continuous twin-screw wet granulation

2019 ◽  
Vol 561 ◽  
pp. 265-273 ◽  
Author(s):  
F. Stauffer ◽  
V. Vanhoorne ◽  
G. Pilcer ◽  
Pierre-François Chavez ◽  
C. Vervaet ◽  
...  
Keyword(s):  
Raw Material ◽  
Wet Granulation ◽  
Twin Screw ◽  
Raw Material Variability

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

Storage Problems of Poplar Chips from Short Rotation Plantations with Special Emphasis on Fungal Development

2012 ◽  
Vol 8 (1) ◽  
pp. 123-132 ◽  
Author(s):  
Zsuzsanna Horváth ◽  
Béla Marosvölgyi ◽  
Christine Idler ◽  
Ralf Pecenka ◽  
Hannes Lenz
Keyword(s):  
Particle Size ◽  
Health Risk ◽  
Dry Matter ◽  
Ph Value ◽  
Wood Chips ◽  
Raw Material ◽  
Special Focus ◽  
Fungal Development ◽  
Short Rotation ◽  
Fungal Particles

Abstract - There are several problems in storing wood chips freshly harvested from short rotation plantations, which result in quality losses as well as in dry matter and energy losses. The factors influencing the degradation of raw material are examined in this paper with special focus on fungal development. An excessive growth of fungi is connected to dry matter losses and also to an increased health risk during raw material handling. The following factors were measured during 6 months storage of poplar wood chips depending on particle size: box temperature, moisture content, pH-value, appearance of fungi in the storage and the concentration of fungal particles in the air. The results show a close connection between particle size, temperature and attack of fungi. During the storage mesophilic and termophilic species of the genera Alternaria, Aspergillus, Cladosporium, Mucor and Penicillium appeared. The concentration of fungal particles is the highest for fine chips and decreases in bigger particles. There was a special focus on the investigation of the properties of coarse chips (G 50), which represent a good compromise between handling, storage losses and health risk due to fungal development.

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 Wire Arc Additive Manufacturing: Review on Recent Findings and Challenges in Industrial Applications and Materials Characterization

Metals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 939
Author(s):  
Mukti Chaturvedi ◽  
Elena Scutelnicu ◽  
Carmen Catalina Rusu ◽  
Luigi Renato Mistodie ◽  
Danut Mihailescu ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Structural Integrity ◽  
Industrial Applications ◽  
Raw Material ◽  
Continuous Increase ◽  
Control Optimization ◽  
Modern Manufacturing ◽  
Directed Energy ◽  
Manufacturing Technologies ◽  
Wire Arc Additive Manufacturing

Wire arc additive manufacturing (WAAM) is a fusion manufacturing process in which the heat energy of an electric arc is employed for melting the electrodes and depositing material layers for wall formation or for simultaneously cladding two materials in order to form a composite structure. This directed energy deposition-arc (DED-arc) method is advantageous and efficient as it produces large parts with structural integrity due to the high deposition rates, reduced wastage of raw material, and low consumption of energy in comparison with the conventional joining processes and other additive manufacturing technologies. These features have resulted in a constant and continuous increase in interest in this modern manufacturing technique which demands further studies to promote new industrial applications. The high demand for WAAM in aerospace, automobile, nuclear, moulds, and dies industries demonstrates compatibility and reflects comprehensiveness. This paper presents a comprehensive review on the evolution, development, and state of the art of WAAM for non-ferrous materials. Key research observations and inferences from the literature reports regarding the WAAM applications, methods employed, process parameter control, optimization and process limitations, as well as mechanical and metallurgical behavior of materials have been analyzed and synthetically discussed in this paper. Information concerning constraints and enhancements of the wire arc additive manufacturing processes to be considered in terms of wider industrial applicability is also presented in the last part of this paper.

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