A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes

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

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2019.06.023 ◽

2019 ◽

Vol 108 (11) ◽

pp. 3502-3514 ◽

Cited By ~ 4

Author(s):

Gabriella Dahlgren ◽

Pirjo Tajarobi ◽

Eric Simone ◽

Brendon Ricart ◽

Jason Melnick ◽

...

Keyword(s):

Control Strategy ◽

Drug Product ◽

Wet Granulation ◽

Twin Screw ◽

Product Manufacturing

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Dynamic analysis of on-line product quality attributes of a food extruder Análisis dinámico de los atributos de calidad de productos extrudados

Food Science and Technology International ◽

10.1177/108201329700300603 ◽

1997 ◽

Vol 3 (6) ◽

pp. 413-421 ◽

Cited By ~ 1

Author(s):

S.L. Schonauer ◽

R.G. Moreira

Keyword(s):

Moisture Content ◽

Product Quality ◽

Bulk Density ◽

Control Variable ◽

Extrusion Process ◽

Quality Attributes ◽

Twin Screw ◽

Primary Driver ◽

Highly Correlated ◽

Non Linear System

The dynamics of a twin screw food extrusion process, including product quality attributes (PQA), to change in feed rate, water rate, screw speed, and barrel temperature at zone 5 were defined. Two PQA variables clearly dominated, colour-b and collet moisture content, which were highly correlated to bulk density. Product temperature at the die also showed high steady-state correla tion with bulk density. Moisture in the barrel was the primary driver for the colour-b and collet moisture content responses. Barrel temperature-5 was important in the response of product temper ature, but excessive delay times made it less important as a control variable. The gains indicated a non-linear system over the response range explored.

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