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Potential of Powder Rheology for Detecting Unforeseen Cross-Contamination of Foreign Active Pharmaceutical Ingredients

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Abstract

Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a slee** drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.

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Data Availability

Data sets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Kei Ariyoshi, Keiji Yuge, Shinya Miyamoto, Ryutaro Nakashima, Ami Yamaguchi, Hiroto Ogata, Koushiro Hirai, Souta Imagawa, and Yuri Hattori, college students working in our laboratory, for providing assistance with the implementation of this study and the results.

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  1. Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka- shi, Fukuoka, 814-0180, Japan

    Shuichi Setoguchi, Shotaro Goto & Kazuhisa Matsunaga

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  1. Shuichi Setoguchi
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Conception or design of the work: Shuichi Setoguchi; Acquisition, analysis, or interpretation of data: Shuichi Setoguchi, Shotaro Goto, and Kazuhisa Matsunaga; Drafting the work or revising it critically for important intellectual content: Shuichi Setoguchi; Final approval of the version to be published: Shuichi Setoguchi, Shotaro Goto, and Kazuhisa Matsunaga; Agreement to be accountable for all aspects of the work: Shuichi Setoguchi, Shotaro Goto, and Kazuhisa Matsunaga.

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Correspondence to Shuichi Setoguchi.

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Setoguchi, S., Goto, S. & Matsunaga, K. Potential of Powder Rheology for Detecting Unforeseen Cross-Contamination of Foreign Active Pharmaceutical Ingredients. AAPS PharmSciTech 25, 138 (2024). https://doi.org/10.1208/s12249-024-02856-0

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