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Chemical imaging analysis of active pharmaceutical ingredient in dissolving microneedle arrays by Raman spectroscopy

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Abstract

The purpose of this study was to develop a quality evaluation method for dissolving microneedle arrays (DMNAs) and determine the spatial distribution pattern of drugs in DMNAs. Raman spectroscopy mapping was used to visualize the drug distribution in DMNAs and drug-loaded polymer films as a model. Powder X-ray diffraction (PXRD) and high-pressure liquid chromatography were also performed to characterize DMNAs. Drug-loaded polymer films and DMNAs were prepared by drying the aqueous solutions spread on the plates or casting. PXRD analysis suggested the crystallization of diclofenac sodium (DCF) in several forms depending on its amount in the sodium hyaluronate (HA)–based films. The Raman spectra of HA and DCF showed characteristic and non-overlapping peaks at 1376 and 1579 cm−1 Raman shifts, respectively. The intensity of the characteristic peak of DCF in the DCF-loaded films increased linearly with the increasing drug content in the range of 4.8 to 16.7% (DCF, w/w). Raman imaging analysis revealed a homogenous dispersion of small DCF crystals in these films. Raman imaging indicates the distribution of DCF on the surface of the DMNA needle. This work highlights the benefit of using Raman spectroscopy mapping to reveal the spatial distribution of drugs in DMNAs.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank Fumio Kamiyama, Kenji Kajiyama, and Ying-Shu Quan from CosMED Pharmaceutical Co. Ltd. for useful discussions.

Funding

This research was supported by JSPS KAKENHI Grant Number JP20K16067 and AMED under Grant Number JP21mk0101193.

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Authors and Affiliations

  1. Division of Drugs, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan

    Daisuke Ando, Tamaki Miyazaki, Eiichi Yamamoto, Tatsuo Koide & Ken-ichi Izutsu

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  1. Daisuke Ando
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  2. Tamaki Miyazaki
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  3. Eiichi Yamamoto
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  4. Tatsuo Koide
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  5. Ken-ichi Izutsu
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Contributions

D.A. designed the study, performed experiments, and wrote the manuscript. T.M. and T.K. assisted with writing the manuscript. E.Y. and K.I. directed the research and assisted in writing and editing the manuscript. All the authors have provided comments on the manuscript.

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Correspondence to Daisuke Ando.

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Ando, D., Miyazaki, T., Yamamoto, E. et al. Chemical imaging analysis of active pharmaceutical ingredient in dissolving microneedle arrays by Raman spectroscopy. Drug Deliv. and Transl. Res. 12, 426–434 (2022). https://doi.org/10.1007/s13346-021-01052-y

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  • DOI: https://doi.org/10.1007/s13346-021-01052-y

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