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Improving Feedability of Highly Adhesive Active Pharmaceutical Ingredients by Silication

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Abstract

Purpose

Loss-in-weight feeders play a vital role in assuring blend and content uniformity as well as lot-to-lot powder traceability in continuous manufacturing. Irregular flow from the feeders propagates through the system, potentially resulting in out-of-specification product. Powder properties such as density, cohesion, and adhesion can cause large variability in the flow rate of ingredients from powder feeders. Feeding of active pharmaceutical ingredients (API) can be difficult because of inherently poor flow, low density, high cohesion, and adhesion.

Method

API was chosen due to known adhesion behavior inside feeders during continuous operations. The selected APIs were blended with nanosized silica, in a V-blender, to provide separation between the API particles and reducing the effect of interparticle forces. The material was characterized by standard pharmaceutical techniques to identify bulk changes between the as-received and the blended API. The coated API was then fed using a Coperion K-Tron KT-20 pharmaceutical loss-in-weight feeder. The material was dispensed onto a catch scale, recording mass versus time, and analyzed for relative standard deviation and deviation from the set point. Additionally, the mass of the remaining API in the feeder after the run ended was compared between the API and silica-blended API.

Results

Blending APIs with nanosized silica successfully improved API feeding performance despite their intrinsic highly adhesive and cohesive behavior. Both the pure and silica-blended APIs were fed using a twin screw powder feeder. When feeding unsilicated APIs, large variability in flow rate and screw speed were observed, and large amounts of material coated the inside of the hopper and screws. When the adhesive APIs were blended with nanosized silica and fed through a loss-in-weight feeder, there was significantly less adhesion to the feeder, and the material was dispensed with significant reduction in flow rate and screw speed variability.

Conclusions

This work provides a means to increase the applicability of continuous manufacturing by enabling the practitioner to manage adverse impact of cohesive material properties on feeder performance. Blending highly adhesive API with silica reduces the adhesion of the API to the feeder hopper and screws, while also improving the deviation in mass flow rate exiting the feeder.

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Acknowledgments

The authors would like to thank Tianyi Li, Kien Chau, Sejal Shah, and Glinka Pereira for their assistance in this work.

Funding

The research was financially supported by the Janssen Ortho LLC.

Author information

Author notes

  1. M. Sebastian Escotet-Espinoza

    Present address: Oral Formulations Science and Technology, Merck & Co. Inc., Rahway, NJ, USA

  2. Sara Moghtadernejad

    Present address: Department of Chemical Engineering, California State University, Long Beach, CA, USA

Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA

    M. Sebastian Escotet-Espinoza, James V. Scicolone, Sara Moghtadernejad, Marianthi Ierapetritou & Fernando J. Muzzio

  2. Advanced Technologies Center of Excellence, Janssen Supply Chain, Gurabo, PR, USA

    Eric Sanchez

  3. Advanced Technologies Center of Excellence, Janssen Supply Chain, Beerse, Belgium

    Philippe Cappuyns & Ivo Van Assche

  4. Drug Product Development, Discovery Product Development and Supply, Janssen Pharmaceutical Companies of Johnson and Johnson, Beerse, Belgium

    Giustino Di Pretoro

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  1. M. Sebastian Escotet-Espinoza
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Correspondence to James V. Scicolone.

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Escotet-Espinoza, M.S., Scicolone, J.V., Moghtadernejad, S. et al. Improving Feedability of Highly Adhesive Active Pharmaceutical Ingredients by Silication. J Pharm Innov 16, 279–292 (2021). https://doi.org/10.1007/s12247-020-09448-y

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