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


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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.Graphical abstractThis work investigates the macro and micro structural material properties of dissolvable microprojections for vaccine delivery, containing common stabilizing sugars and polyols. This uses a range of techniques (microscopy, nanoindentation, synchrotron FT-FIR) to measure material modulus, projection strength, projection amorphous/crystalline structure, as well skin penetration, dissolution and diffusion. This uniquely shows the impact of pharmaceutical stabilisers on microdevice manufacture/function.

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