Development of an Orodispersible Film Containing Stabilized Influenza Vaccine.

Abstract

Most influenza vaccines are administered via injection, which is considered as user-unfriendly. Vaccination via oral cavity using an orodispersible film (ODF) might be a promising alternative. To maintain the antigenicity of the vaccine during preparation and subsequent storage of these ODFs, sugars such as trehalose and pullulan can be employed as stabilizing excipients for the antigens. In this study, first, β-galactosidase was used as a model antigen. Solutions containing β-galactosidase and sugar (trehalose or trehalose/pullulan blends) were pipetted onto plain ODFs and then either air- or vacuum-dried. Subsequently, sugar ratios yielding the highest β-galactosidase stability were used to prepare ODFs containing H5N1 whole inactivated influenza virus vaccine (WIV). The stability of the H5N1 hemagglutinin was assessed by measuring its hemagglutination activity. Overall, various compositions of trehalose and pullulan successfully stabilized β-galactosidase and WIV in ODFs. WIV incorporated in ODFs showed excellent stability even at challenging storage conditions (60 °C/0% relative humidity or 30 °C/56% relative humidity) for 4 weeks. Except for sugars, the polymeric component of ODFs, i.e., hypromellose, possibly improved stability of WIV as well. In conclusion, ODFs may be suitable for delivering of WIV to the oral cavity and can possibly serve as an alternative for injections.