Stress factors affecting protein stability during the fabrication and storage of dissolvable microneedles

Abstract

Abstract Objectives The current review summarizes product and process attributes that were reported to influence protein integrity during manufacturing and storage of dissolvable microneedle arrays. It also discusses challenges in employing established protein characterization methods in dissolvable microneedle formulations. Methods Studies on dissolvable microneedles loaded with protein therapeutics that assess protein stability during or after fabrication and storage were collected. Publications addressing other types of microneedles, such as coated and vaccine-loaded microneedles, are also discussed as they face similar stability challenges. Key findings To date, various researchers have successfully incorporated proteins in dissolvable microneedles, but few publications explicitly investigated the impact of formulation and process parameters on protein stability. However, protein therapeutics are exposed to multiple thermal, physical, and chemical stressors during the fabrication and storage of microneedles. These stressors include increased temperature, shear and interfacial stress, transition to the solid state during drying, interaction with excipients, and suboptimal pH environments. While analytical methods are essential for monitoring protein integrity during manufacturing and storage, the performance of some well-established protein characterization techniques can be undermined by polymer excipients commonly employed in dissolvable microneedle formulations. Conclusions It is essential to understand the impact of key process and formulation parameters on the stability of protein therapeutics to facilitate their safe and effective administration by dissolvable microneedles.