Effect of protein release rates from tablet formulations on the immune response after sublingual immunization.

Dry vaccine formulations for sublingual administration would provide great advantages for public health use, especially in developing countries, since they are easy to administer and might also have improved stability properties. This study investigates the influence of protein release rate from mucoadhesive two-layer tablets on the elicited antibody responses after sublingual immunization. Two fast release tablets, one based on a mixture of lactose and microcrystalline cellulose (MCC) and one protein coated ethylcellulose (EC) tablet, and three hydrophilic matrix tablets with extended release (ER) properties based on HPMC 90 SH 100000 or Carbopol® 974-P NF were tested. The in vitro release profiles of the model protein ovalbumin (OVA) from these tablets were characterized and correlated to the in vivo potential of the tablets to induce an immune response after sublingual immunization in BALB/c mice. It could be concluded that a tablet with fast protein release elicits antibody titres not significantly different from titres obtained with OVA in solution, whereas low immune responses were observed with a slow release of OVA from the ER formulations. Thus, an ER tablet seems not favorable for vaccine delivery to the sublingual mucosa. Thus, we can present a fast releasing tablet formulation with attractive features for sublingual immunization, whereas the use of ER formulations for sublingual vaccination has to be investigated more in detail.