Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior

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.

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Evaluation of Binders in Twin-Screw Wet Granulation

Pharmaceutics ◽

10.3390/pharmaceutics13020241 ◽

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13020210 ◽

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.

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