Influence of protein on mannitol polymorphic form produced during co-spray drying

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Excipient effects on therapeutic proteins are widely studied.
• The reciprocal influence of proteins on excipient properties remains less explored.
• Understanding these interactions is crucial for drug formulation and stability.

Purpose of the Study:

• To investigate the impact of two model proteins on mannitol polymorphism during spray drying.
• To analyze the structural and thermal properties of spray-dried mannitol/protein blends.
• To assess the long-term storage stability of these formulations.

Main Methods:

• Spray drying of mannitol/protein blends.
• Structural characterization using X-ray powder diffraction (XRPD) and Fourier transform Raman spectroscopy (FT-Raman).
• Thermal analysis via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).
• Storage stability assessment under elevated temperature and relative humidity (RH).

Main Results:

• Mannitol's solid-state form (amorphous or crystalline) post-spray drying was dependent on the co-processed protein.
• Upon storage, different mannitol polymorphic forms (beta and delta) emerged, influenced by the specific protein.
• The protein exhibited a polymorph-directing effect on mannitol.

Conclusions:

• Protein-excipient interactions significantly influence mannitol's polymorphic behavior during spray drying and storage.
• Relative water levels, affected by co-solute effects, are a key factor in directing mannitol's polymorph.
• This finding has implications for optimizing drug product stability and formulation design.