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Purpose <p>Drying is widely used to enhance the storage stability of biologic drug products which are susceptible to degradation in aqueous solutions. Compared to conventional freeze-drying, spray drying offers continuous, high-throughput manufacturing. Stabilizing excipients are critical for protecting proteins from stresses during drying and storage. This study evaluated the potential of polysaccharide- and protein-lysate–based polymeric excipients as alternatives to commonly used stabilizers such as trehalose and mannitol, using bovine serum albumin (BSA) as a model protein.</p> Methods <p>Spray-dried BSA formulations were prepared with (2-hydroxypropyl)-β-cyclodextrin (HPβCD), hydrolyzed gelatin, dextran 20&#xa0;kDa, or sodium carboxymethyl cellulose (NaCMC) polymers, either alone or in combination with trehalose or mannitol. Protein stability was assessed by monitoring monomer loss under stressed storage (40°C, 3&#xa0;months). Crystallinity and changes in the secondary structure were analyzed using powder X-ray diffraction (PXRD) and solid-state Fourier transform infrared spectroscopy (ssFTIR), respectively. Particle size and size distribution, surface morphology and reconstitution time were also evaluated.</p> Results <p>Spray-dried BSA formulations containing HPβCD or hydrolyzed gelatin, either alone or with sugars, exhibited lower monomer loss than the trehalose- or mannitol-only formulations. In contrast, formulations with Dextran 20&#xa0;kDa and NaCMC showed poor stability. PXRD revealed progressive sodium chloride crystallization during storage. ssFTIR detected secondary structure changes in the BSA over 3&#xa0;months. The spray-dried powders with polysaccharides generally showed longer reconstitution times than those with polymers.</p> Conclusion <p>HPβCD and hydrolyzed gelatin improved the physical stability of spray-dried BSA compared to sugar excipients, which highlights their potential use as stabilizing additives.</p>

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Polymers as Stabilizing Excipients for Spray-Dried Protein Formulations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月23日

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  • Chanakya D. Patil,
  • Yijing Huang,
  • Kinnari Santosh Arte,
  • Navin Kafle,
  • Harshil K. Renawala,
  • Jiaying Liu,
  • Haichen Nie,
  • Qi Tony Zhou,
  • Li Lily Qu

摘要

Purpose

Drying is widely used to enhance the storage stability of biologic drug products which are susceptible to degradation in aqueous solutions. Compared to conventional freeze-drying, spray drying offers continuous, high-throughput manufacturing. Stabilizing excipients are critical for protecting proteins from stresses during drying and storage. This study evaluated the potential of polysaccharide- and protein-lysate–based polymeric excipients as alternatives to commonly used stabilizers such as trehalose and mannitol, using bovine serum albumin (BSA) as a model protein.

Methods

Spray-dried BSA formulations were prepared with (2-hydroxypropyl)-β-cyclodextrin (HPβCD), hydrolyzed gelatin, dextran 20 kDa, or sodium carboxymethyl cellulose (NaCMC) polymers, either alone or in combination with trehalose or mannitol. Protein stability was assessed by monitoring monomer loss under stressed storage (40°C, 3 months). Crystallinity and changes in the secondary structure were analyzed using powder X-ray diffraction (PXRD) and solid-state Fourier transform infrared spectroscopy (ssFTIR), respectively. Particle size and size distribution, surface morphology and reconstitution time were also evaluated.

Results

Spray-dried BSA formulations containing HPβCD or hydrolyzed gelatin, either alone or with sugars, exhibited lower monomer loss than the trehalose- or mannitol-only formulations. In contrast, formulations with Dextran 20 kDa and NaCMC showed poor stability. PXRD revealed progressive sodium chloride crystallization during storage. ssFTIR detected secondary structure changes in the BSA over 3 months. The spray-dried powders with polysaccharides generally showed longer reconstitution times than those with polymers.

Conclusion

HPβCD and hydrolyzed gelatin improved the physical stability of spray-dried BSA compared to sugar excipients, which highlights their potential use as stabilizing additives.