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.

Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

“…The hemagglutination assay of WIV was performed as previously described 29,30 . Briefly, WIV incorporated in dMNAs was reconstituted in PB (10mM, pH 7.4).…”

Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems

“…Thus, hindering the access to affordable vaccines for many low-income countries with limited cold chain logistics, leading to suboptimal immunizations. Vaccine development in oral dosage forms such as films [73,115] and microneedle arrays [77] have been shown to maintain its stability even under extreme conditions. These systems could be loaded with antigen particles that are found as dry powder.…”

“…The oral cavity shows great potential for antigen delivery. Various dosage forms have been developed that use the oral cavity as the site of administration, with tablets [71], mucoadhesive films [5,6,[71][72][73], gels [74], microneedles [75][76][77][78], and MucoJet™ [79] being reported (Table 2). The routes that comprise the oral cavity can be beneficial in many cases, increasing patient compliance because of its ease of administration and allowing a large-scale immunization.…”

Nanocarriers-Assisted Needle-Free Vaccine Delivery Through Oral and Intranasal Transmucosal Routes: A Novel Therapeutic Conduit

“…When the efficacy and release of microneedles and disks were compared, it was found that the microneedles were able to diffuse mucosal layer in 20 min, while disks diffused very slowly and should be in the contact with mucosa for several hours. In another study, an orodispersible film (ODF) containing H5N1 whole inactivated influenza virus vaccine was developed ( Tian et al, 2020 ). Sugars such as trehalose and pullulan were used as stabilizing excipients which helped in maintaining the antigenicity of vaccine during preparation as well as during storage.…”