Blends of trehalose and pullulan to stabilize biopharmaceuticals in alternative dosage forms: orodispersible films and dissolving microneedles

Yu Tian

Research output: ThesisThesis fully internal (DIV)

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Biopharmaceuticals, e.g. proteins and vaccines, have become the fastest growing class of medicines in today’s pharmaceutical markets. However, a broader application of biopharmaceuticals is hampered by two major challenges, i.e. instability of these products and limitations with respect to the route of administration. In this PhD-study, possible solutions for these two challenges were investigated.
Biopharmaceuticals can be stabilized by drying them in the presence of sugars. We found that using a combination of a low molecular weight sugar (trehalose) and a high molecular weight polysaccharide (pullulan) provided excellent stability to beta-galactosidase (a model protein) during drying and storage in particular when exposed to high humidities. These results were ascribed to the ability of trehalose to form a compact coating around the protein and the excellent physical properties of pullulan.
Most biopharmaceuticals are administrated via injection, which harbors several drawbacks. Therefore, in this PhD-study two alternative dosage forms have been explored. Amongst other biopharmaceuticals, whole inactivated influenza virus vaccine (WIV), was incorporated in either orodispersible films (ODFs) for oral administration or dissolving microneedles for intradermal delivery. Trehalose and pullulan were employed as stabilizing excipients. WIV showed very good stability during preparation of both of these alternative dosage forms and during subsequent storage. Furthermore, the ODFs showed the required mechanical properties and fast dissolution behavior. Also, the microneedles showed the required mechanical properties as they could efficiently penetrate human skin ex vivo. Future in vivo experiments have to show the potential of these two dosage forms.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
  • Frijlink, Erik, Supervisor
  • Hinrichs, Wouter, Co-supervisor
Award date23-Oct-2020
Place of Publication[Groningen]
Publication statusPublished - 2020

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