Addition of Pullulan to Trehalose Glasses Improves the Stability of ß-Galactosidase at High Moisture Conditions.

Incorporation of therapeutic proteins in a matrix of sugar glass is known to enhance protein stability, yet protection is often lost when exposed to high relative humidity (RH). We hypothesized that especially in these conditions the use of binary glasses of a polysaccharide and disaccharide might yield advantages for protein stability. Therefore, different amounts of the polysaccharide pullulan were introduced in freeze-dried trehalose glasses. In these homogeneous blends, the presence of pullulan above 50 weight % prevented crystallization of trehalose when exposed to high RH. Storage stability testing up to 4 weeks of the model protein ß-galactosidase incorporated in pullulan/trehalose blends showed superior behavior of pure trehalose at 30°C/0% RH, while pullulan/trehalose blends yielded the best stability at 30°C/56% RH. In conclusion, binary glasses of pullulan and trehalose may provide excellent stability of proteins under storage conditions that may occur in practice, namely high temperature and high RH.

Production methods and stabilization strategies for polymer-based nanoparticles and microparticles for parenteral delivery of peptides and proteins.

INTRODUCTION: Therapeutic proteins and peptides often require parenteral administration, which compels frequent administration and patient discomfort. This ultimately decreases compliance and leads to therapy failure. Biocompatible and biodegradable polymers offer a versatile matrix for particles suitable for the parenteral delivery of these biomacromolecules, with the added possibility of long-term controlled release. During the past decade, research on polymeric microparticles and nanoparticles as delivery vehicles has intensified; nevertheless, only few products have been commercialized. AREAS COVERED: This review discusses the different production techniques for microparticles and nanoparticles suitable for peptide and protein delivery, including examples of recently developed formulations. Stability of the biomacromolecules related to these production techniques is evaluated, as it is a critical parameter to be considered during product development. Additionally, several strategies to improve stability are described in detail, providing insight and guidance for further formulation development. EXPERT OPINION: In the conventionally used and thoroughly investigated emulsification method, stability of peptides and proteins is still a challenge. Emerging methods like solvent displacement, layer-by-layer polymer deposition, electrospraying and supercritical fluid technologies have the potential to improve stability of the protein and peptide. Nonetheless, these methods are still under development and they need critical evaluation to improve production efficiency before proceeding to in vivo efficacy studies. Improvement should be achieved by strengthening cooperation between academic research groups, pharmaceutical companies and regulatory authorities.