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

The stabilizing ability of the excipient on pharmaceutically relevant proteins for potential therapeutic use is an extensive area of research but the effect the protein has on the excipient is rarely reported. The influence of two model proteins on the polymorphic behaviour of mannitol during spray drying was therefore investigated. Spray dried mannitol/protein blends were characterised structurally using X-ray powder diffraction (XRPD) and Fourier transform Raman spectroscopy (FT-Raman) and thermally by differential scanning calorimetry (DSC) and also thermogravimetric analysis (TGA). To assess the long term storage stability, samples were subjected to conditions of elevated temperature and relative humidity (RH). Structural and thermal analysis of the samples showed that upon spray drying mannitol could be completely amorphous or crystalline dependent on the protein co-spray dried. Upon storage at elevated temperature and RH different polymorphic forms of mannitol (beta and delta) were evident again dependent on the protein co-spray dried. Under the conditions employed there was a polymorph directing effect on mannitol dependent on the protein with which it was co-spray dried with co-solute effects on relative water levels being indicated as a major factor in directing the polymorph.