“Rolling” phenomenon in twin screw granulation with controlled-release excipients

Abstract

The developed knowledge regarding use of twin screw granulators for continuous wet granulation has been primarily limited to immediate release formulations in the literature. The present study highlights an issue previously unreported for wet granulation with twin screw extruders when using formulations containing controlled-release (CR) excipients. Long (3–10 mm), twisted noodle-like granules can be produced in the presence of these excipients that are difficult to control and are anticipated to create complications in downstream unit operations to the granulator. Working with two different CR excipients, METHOCEL™ K4M and Kollidon® SR, each blended at different ratios with a mixture of 80% α-lactose monohydrate/20% microcrystalline cellulose, these unique particles were found to be produced in the conveying elements of the extruder, arising from a rolling action at the top of the screw flights. The CR excipients adhesively strengthen the wetted mass, forming this undesired granule shape such that they persisted to the exit of the machine; the shape appeared most strongly affected by screw speed, producing particles of higher aspect ratio as speed was increased. Adjusting the concentration of these CR excipients in the formulation, the flow rate or the type of compression element used in the screws proved ineffective in controlling the problem. Rather, a re-design of the extruder screws was required to prevent generation of these extended-form granules.

• Continuous granulation
• controlled-release
• foam
• rolling
• twin screw extruder

Acknowledgements

The authors would like to extend their thanks to the Natural Sciences and Engineering Research Council of Canada for their funding of this project and to The Dow Chemical Company for their technical advice and donation of materials. Additional thanks to Ms Huiying Li who ran the experiment concerning the influence of flow rate and provided some analysis of the samples discussed in this work.

Declaration of interest

The authors would like to extend their thanks to the Natural Sciences and Engineering Research Council of Canada for their funding of this project and to The Dow Chemical Company for their technical advice and donation of materials. All authors of this manuscript declare no conflicts of interest.