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Fabrication of pure-drug microneedles for delivery of montelukast sodium

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Abstract

Dissolving microneedle (MN) patches are usually formulated with a blend of drug and excipients added for mechanical strength and drug stabilization. In this study, we developed MNs made of pure drug to maximize drug loading capacity. MN patches were fabricated for transdermal delivery of montelukast sodium (MS) which is used to treat asthma and allergic rhinitis. We developed three different fabrication methods — solvent casting, melt casting, and solvent washing — and determined that filling molds with MS powder followed by a solvent washing method enabled MS to be loaded selectively to the MNs. Drug localization was confirmed with Raman imaging. MNs were able to penetrate in vitro and ex vivo skin models, and maintained strong mechanical properties during 6 months’ storage at 22 °C. MS was also stable and compatible with the formulation used for the patch backing layer after 3 months’ storage at 40 °C. MS delivery efficiency into skin was 55%, which enabled delivery of 3.2 mg MS into porcine skin ex vivo, which is in the range of MS doses in human clinical use. We conclude that the solvent washing method can be used to prepare MNs containing pure drug, such as MS at milligram doses in a ~ 1 cm2 MN patch.

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Acknowledgements

We thank Dr. Richard Terry for technical advice related to hydrogels and Donna Bondy for administrative support.

Funding

This work was supported by The Scientific and Technological Research Council of Turkey-TÜBİTAK (2214-A—International Research Fellowship Programme for PhD Students).

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Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Erkan Azizoglu & Mark R. Prausnitz

  2. Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, 35040, Bornova, Izmir, Turkey

    Erkan Azizoglu & Ozgen Ozer

Authors
  1. Erkan Azizoglu
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  2. Ozgen Ozer
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  3. Mark R. Prausnitz
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Contributions

Erkan Azizoglu: conceptualization, methodology, validation, investigation, formal analysis, data curation, writing—original draft, visualization, funding acquisition. Ozgen Ozer: conceptualization, supervision. Mark R. Prausnitz: conceptualization, methodology, resources, writing—review and editing, supervision, project administration.

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Correspondence to Mark R. Prausnitz.

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Conflict of interest

Mark R Prausnitz is an inventor of microneedle patents, is a paid advisor, and is a founder/shareholder of companies developing microneedle-based products (Micron Biomedical). This potential conflict of interest has been disclosed and is managed by Georgia Tech.

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Azizoglu, E., Ozer, O. & Prausnitz, M.R. Fabrication of pure-drug microneedles for delivery of montelukast sodium. Drug Deliv. and Transl. Res. 12, 444–458 (2022). https://doi.org/10.1007/s13346-021-01047-9

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