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A Non-destructive Quantitative Transmission Raman Spectroscopy Method for Active Pharmaceutical Ingredient in Drug Product In-Use Samples Prepared in Dosing Vehicles

Abstract

Compatibility and in-use stability screening studies are required for dosing vehicle selection based on the FDA’s guidance, “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments.” One of the major analytical challenges in these studies is sample preparation because extracting active pharmaceutical ingredient (API) from the drug product mixed into viscous soft-food matrices (e.g., yogurt or apple sauce) is laborious, prone to human errors, and time-consuming. Additionally, observed in-solution degradation caused by dosing vehicle ingredients causes analytical error. In our study, NIR- and Raman-based non-destructive tests have been explored and developed with drug product powder formulation prepared in dosing vehicles. A transmission Raman chemometrics model was developed and calibrated with samples varying in API content, water content, and milled extrudate particle size distribution. The method was proven to be accurate, linear, selective, and robust. Our work with non-destructive tests eases the laboratory burdens to perform in-use stability studies with dosing vehicles for all phases of development that need to cover all application scenarios of clinical preparation and usage.

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Acknowledgements

The authors would like to thank Julia Griffen and Matthew Bloomfield from Agilent (Cobalt).

Funding

The design, study conduct, and financial support for this research were provided by AbbVie.  

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Authors and Affiliations

Authors

Contributions

Gregory Doddridge: conceptualization, designing, testing, writing, reviewing, and editing. Edwin Hong: designing, testing, writing, reviewing, and editing. David Cheng Thiam Tan: designing, writing, reviewing, and editing. Yemin Liu: conceptualization, designing, writing, reviewing, and editing.

Corresponding author

Correspondence to Yemin Liu.

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Conflict of Interest

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Gregory Doddridge, Edwin Hong, David Cheng Thiam Tan, and Yemin Liu are employees of AbbVie and may own AbbVie stock. AbbVie sponsored the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.

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Doddridge, G., Hong, E., Tan, D.C.T. et al. A Non-destructive Quantitative Transmission Raman Spectroscopy Method for Active Pharmaceutical Ingredient in Drug Product In-Use Samples Prepared in Dosing Vehicles. AAPS PharmSciTech 23, 132 (2022). https://doi.org/10.1208/s12249-022-02286-w

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  • DOI: https://doi.org/10.1208/s12249-022-02286-w

KEY WORDS

  • non-destructive
  • dosing vehicles
  • in-use samples
  • chemometrics
  • transmission Raman spectroscopy