Polymers as Stabilizing Excipients for Spray-Dried Protein Formulations

Area of Science:

• Pharmaceutical Sciences
• Biotechnology
• Materials Science

Background:

• Biologic drug products require stabilization during storage, often achieved through drying techniques.
• Spray drying is a high-throughput alternative to freeze-drying for enhancing drug product stability.
• Stabilizing excipients are crucial for protecting sensitive proteins from degradation during processing and storage.

Purpose of the Study:

• To evaluate polysaccharide- and protein-lysate-based polymeric excipients as alternatives to conventional stabilizers like trehalose and mannitol.
• To assess the stabilizing potential of (2-hydroxypropyl)-β-cyclodextrin (HPβCD) and hydrolyzed gelatin for spray-dried bovine serum albumin (BSA).
• To compare the efficacy of novel excipients against traditional sugar stabilizers for protein protection during spray drying and storage.

Main Methods:

• Preparation of spray-dried BSA formulations using HPβCD, hydrolyzed gelatin, dextran 20 kDa, or sodium carboxymethyl cellulose (NaCMC), with or without trehalose or mannitol.
• Assessment of protein stability by monitoring monomer loss under stressed storage conditions (40°C for 3 months).
• Analysis of crystallinity (PXRD), secondary structure changes (ssFTIR), particle characteristics, and reconstitution times.

Main Results:

• Formulations with HPβCD or hydrolyzed gelatin demonstrated significantly lower BSA monomer loss compared to trehalose or mannitol alone.
• Dextran 20 kDa and NaCMC formulations exhibited poor protein stability.
• Powder X-ray diffraction revealed salt crystallization, and solid-state Fourier transform infrared spectroscopy indicated secondary structure changes in BSA over time.

Conclusions:

• HPβCD and hydrolyzed gelatin effectively improved the physical stability of spray-dried BSA.
• These polymeric excipients show potential as superior stabilizing additives compared to traditional sugar-based stabilizers.
• The findings support the use of HPβCD and hydrolyzed gelatin for enhancing the stability of protein-based pharmaceuticals.