Formulations for microprojection/microneedle vaccine delivery: Structure, strength and release profiles

Anthony P. Raphael, Michael L. Crichton, Robert J. Falconer, Stefano Meliga, Xianfeng Chen, Germain J.P. Fernando, Han Huang, Mark A.F. Kendall

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

To develop novel methods for vaccine delivery, the skin is viewed as a high potential target, due to the abundance of immune cells that reside therein. One method, the use of dissolving microneedle technologies, has the potential to achieve this, with a range of formulations now being employed. Within this paper we assemble a range of methods (including FT-FIR using synchrotron radiation, nanoindentation and skin delivery assays) to systematically examine the effect of key bulking agents/excipients - sugars/polyols - on the material form, structure, strength, failure properties, diffusion and dissolution for dissolving microdevices. We investigated concentrations of mannitol, sucrose, trehalose and sorbitol from 1:1 to 30:1 with carboxymethylcellulose (CMC), although mannitol did not form our micro-structures so was discounted early in the study. The other formulations showed a variety of crystalline (sorbitol) and amorphous (sucrose, trehalose) structures, when investigated using Fourier transform far infra-red (FT-FIR) with synchrotron radiation. The crystalline structures had a higher elastic modulus than the amorphous formulations (8-12 GPa compared to 0.05-11 GPa), with sorbitol formulations showing a bimodal distribution of results including both amorphous and crystalline behaviour. In skin, diffusion properties were similar among all formulations with dissolution occurring within 5 s for our small projection array structures (~ 100 μm in length). Overall, slight variations in formulation can significantly change the ability of our projections to perform their required function, making the choice of bulking/vaccine stabilising agents of great importance for these devices.

Original languageEnglish
Pages (from-to)40-52
Number of pages13
JournalJournal of Controlled Release
Volume225
DOIs
Publication statusPublished - 10 Mar 2016

Keywords

  • Drug delivery
  • Formulation
  • Microneedles
  • Skin
  • Vaccine

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Raphael, A. P., Crichton, M. L., Falconer, R. J., Meliga, S., Chen, X., Fernando, G. J. P., Huang, H., & Kendall, M. A. F. (2016). Formulations for microprojection/microneedle vaccine delivery: Structure, strength and release profiles. Journal of Controlled Release, 225, 40-52. https://doi.org/10.1016/j.jconrel.2016.01.027