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Optimization of Spray-Drying Parameters for Formulation Development at Preclinical Scale

  • Research Article
  • Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability
  • Published:
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Abstract

Spray-drying dispersion (SDD) is a well-established manufacturing technique used to prepare amorphous solid dispersions (ASDs), allowing for poorly soluble drugs to have improved bioavailability. However, the process of spray-drying with multiple factors and numerous variables can lead to a lengthy development timeline with intense resource requirements, which becomes the main obstacle limiting spray-drying development at the preclinical stage. The purpose of this work was to identify optimized preset parameters for spray-drying to support the early development of ASDs suitable for most circumstances rather than individual optimization. First, a mini-DoE (Design of Experiment) study was designed to evaluate the critical interplay of two key variables for spray-drying using a BUCHI B-290 mini spray dryer: solid load and atomizing spray gas flow. The critical quality attributes (CQAs) of the ASDs, including yield, particle size, morphology, and in vitro release profile, were taken into account to identify the impact of the key variables. The mini-DoE results indicated that a 5% solid load (w/v %) and 35 mm height atomizing spray gas flow were the most optimized parameters. These predefined values were further verified using different formulation compositions, including various polymers (Eudragit L100-55, HPMCAS-MF, PVAP, and PVP-VA64) and drugs (G-F, GEN-A, Indomethacin, and Griseofulvin), a range of drug loading (10 to 40%), and scale (200 mg to 200 g). Using these predefined parameters, all ASD formulations resulted in good yields as well as consistent particle size distribution. This was despite the differences in the formulations, making this a valuable and rapid approach ideal for early development. This strategy of leveraging the preset spray-drying parameters was able to successfully translate into a reproducible and efficient spray-drying platform while also saving material and reducing developmental timelines in early-stage formulation development.

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Acknowledgements

The authors would like to thank Edward Yost, Evelyn Yanez, Nivedita Shetty, Steven Castleberry, Wei Zhang, Jonathan Hau, Wei Jia, and Yingqing Ran for their support throughout this project.

Funding

This research was funded by Genentech Inc.

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Authors and Affiliations

  1. Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California, 94080, USA

    Marika Nespi, Robert Kuhn, Chun-Wan Yen, Joseph W. Lubach & Dennis Leung

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  1. Marika Nespi
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  2. Robert Kuhn
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  3. Chun-Wan Yen
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  4. Joseph W. Lubach
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  5. Dennis Leung
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Contributions

Marika Nespi: conceptualization, analysis, investigation, methodology, validation, and writing.

Robert Kuhn: analysis, investigation, validation, and writing.

Chun-Wan Yen: conceptualization, analysis, methodology, validation, supervision, and writing.

Joseph W. Lubach: investigation, review and editing.

Dennis Leung: supervision, resources, review and editing.

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Correspondence to Chun-Wan Yen.

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Nespi, M., Kuhn, R., Yen, CW. et al. Optimization of Spray-Drying Parameters for Formulation Development at Preclinical Scale. AAPS PharmSciTech 23, 28 (2022). https://doi.org/10.1208/s12249-021-02160-1

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  • DOI: https://doi.org/10.1208/s12249-021-02160-1

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