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 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.

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 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.

Definition of a JA-2 Equivalent Propellant to be Produced by Continuous Solventless Extrusion

2013 ◽  
Vol 80 (3) ◽  
Author(s):  
Thelma G. Manning ◽  
Joseph Leone ◽  
Martijn Zebregs ◽  
Dinesh R. Ramlal ◽  
Chris A. van Driel
Keyword(s):  
Extrusion Process ◽  
Continuous Manufacturing ◽  
Twin Screw Extrusion ◽  
Extrusion Processing ◽  
Roll Mill ◽  
Screw Extrusion ◽  
Twin Screw ◽  
Ballistic Properties ◽  
Definition Of ◽  
Double Base

In order to eliminate residual solvents in ammunition and to reduce the emissions of volatile organic compounds to the atmosphere, the U.S. Army ARDEC has teamed with TNO in developing a new process for the production of solventless propellant for tank ammunition. To reduce the costs of solventless propellants production, shear roll mill and continuous extrusion processing was investigated. As described in this paper JA-2 a double base propellant cannot be processed without solvent by the extrusion process. An alternative JA-2 equivalent propellant was defined. The aim of this work is to demonstrate the manufacturing of this propellant by solventless continuous twin screw extrusion processing while maintaining gun performance characteristics of conventional JA-2 propellant. This is elucidated by explicitly researching the relationship between interior ballistic properties of the gun propellant and utilizing a continuous manufacturing process. Processing conditions were established, and the propellant was manufactured accordingly. The extruded propellant has the desired properties, which resulted in a comparable gun performance as the conventional JA-2 propellant.

scholarly journals Metamorphosis of Twin Screw Extruder-Based Granulation Technology: Applications Focusing on Its Impact on Conventional Granulation Technology

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Rajat Radhakrishna Rao ◽  
Abhijeet Pandey ◽  
Aswathi R. Hegde ◽  
Vijay Induvadan Kulkarni ◽  
Chetan Chincholi ◽  
...  
Keyword(s):  
Process Analytical Technology ◽  
Twin Screw Extruder ◽  
Continuous Manufacturing ◽  
Screw Extruder ◽  
Solid Dosage ◽  
Regulatory Standards ◽  
Technology Applications ◽  
Twin Screw ◽  
Extrusion Technology ◽  
Granulation Technology

AbstractIn order to be at pace with the market requirements of solid dosage forms and regulatory standards, a transformation towards systematic processing using continuous manufacturing (CM) and automated model-based control is being thought through for its fundamental advantages over conventional batch manufacturing. CM eliminates the key gaps through the integration of various processes while preserving quality attributes via the use of process analytical technology (PAT). The twin screw extruder (TSE) is one such equipment adopted by the pharmaceutical industry as a substitute for the traditional batch granulation process. Various types of granulation techniques using twin screw extrusion technology have been explored in the article. Furthermore, individual components of a TSE and their conjugation with PAT tools and the advancements and applications in the field of nutraceuticals and nanotechnology have also been discussed. Thus, the future of granulation lies on the shoulders of continuous TSE, where it can be coupled with computational mathematical studies to mitigate its complications.

Sign in / Sign up

Export Citation Format

Share Document