414998 Investigation of a Suitable Lubricant for Increasing Slip in a Continuous, Co-Rotating Twin Screw Dry Granulation Process

Wednesday, November 11, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Steve Pafiakis1, John Jones2, Megerle Escotet1, Rekha Keluskar1, Kyle Martin1, Jade Trinh1, Christopher Levins1, Brenda Remy1, Howard Stamato1, Nikolaos Ioannidis3, Chong Peng3 and Costas G. Gogos3, (1)Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, NJ, (2)Drug Product Science and Technology, Bristol-Myers Squibb, Moreton, United Kingdom, (3)Polymer Processing Institute, Newark, NJ

Investigation of a Suitable Lubricant for Increasing Slip in a Continuous, Co-Rotating Twin Screw Dry Granulation Process

Granulating technologies are generally described in two categories: wet and dry. Wet methods apply solution on top of an agitated powder bed. Dry methods compact powders into agglomerates; for example feeding powders through two counter rotating rolls under pressure such that the powders press together to form a thin wafer that is milled into the granulation.

Recently, the industry and universities interested in pharmaceutical processing shifted focus towards continuous granulating technology and the flexibility this technology offers. Many institutions are taking advantage of equipment readily available within their network and for this reason co-rotating twin screw extruders are currently being investigated more intensively. While often considered for making amorphous composites, because of their versatility, they can be efficient continuous granulators.

The preference when granulating with a co-rotating twin screw extruder is to employ a wet granulation method when possible. In this technique, powder is fed into the extruder and conveyed towards a mixing block via two co-rotating screws while being sprayed with a binder solution. The binder solution facilitates granulation upon compaction in the kneading zone. The granules are subsequently dried either down the barrel of the extruder, or externally in by a fluidized bed. The granule attributes are strongly dependant on the binder addition rate, screw speed, and mixing block design.

In the case for dry twin screw granulation a binder solution is not used.  Instead the material is softened using the barrel heating mechanism of the extruder and the energy created by mixing. Agglomerate creation is facilitated by compaction of the soften binder. The granule attributes are strongly dependant on barrel heating/cooling temperature, screw speed, feed rate, and the screw design.

Experiments have shown that the density of the granulation is proportional to the energy applied to the granule. The applied energy can be sufficient to induce degradation in the active pharmaceutical ingredient (API).  Furthermore, for highly cohesive, low bulk density pre-blends, fast screw speeds are required to convey the powder to the granulating zone while maintaining the same feed rate from batch to batch.  The faster screw speeds result in additional energy input with the potential for excessive temperature generation attributed to plastic and frictional energy dissipation (PED and FED).

Evidence of these phenomena is shown by significant shifts in the steady state of the system parameters (e.g. torque, specific energy, and product temperature). Physical observations indicate adhesion of product on the screws in the vicinity of the mixing element with the potential for longer residence times and exposure to heat. Recent experiments have shown that it is possible to reduce these adverse effects of intensive mixing and shear through cooling at the mixing zone.

In addition to cooling at the mixing zone, the shear can further be reduced by adding a suitable level of lubricant, in the pre-blend, that is compatible with the active pharmaceutical ingredient (API).  The lubricant allows a desirable amount of slip between the powder and the equipment surfaces.  The lubrication results in lower torque readings an indication of lower energy absorbed by the product.  The level of lubricant should not compromise the structural integrity of the granule or any downstream granule process. Levels of up to 1.0% magnesium stearate have been shown to reduce the torque in small scale twin-screw granulation trials.

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See more of this Session: Poster Session: Pharmaceutical
See more of this Group/Topical: Pharmaceutical Discovery, Development and Manufacturing Forum