Abstract
PURPOSE: This study aimed to investigate the effect of a model protein on the solid state of a commonly used bulk agent in spray-dried formulations.
METHODS: A series of lysozyme/mannitol formulations were spray-dried using a lab-scale spray dryer. Further, the surface temperature of drying droplet/particles was monitored using the DRYING KINETICS ANALYZER™ (DKA) with controllable drying conditions mimicking the spray-drying process to estimate the drying kinetics of the lysozyme/mannitol formulations. The mannitol polymorphism and the spatial distribution of lysozyme in the particles were examined using X-ray powder diffractometry (XRPD) and Raman microscopy. Partial Least Squares Discriminant Analysis was used for analyzing the Raman microscopy data.
RESULTS: XRPD results indicated that a mixture of β-mannitol and α-mannitol was produced in the spray-drying process which was supported by the Raman analysis, whereas Raman analysis indicated that a mixture of α-mannitol and δ-mannitol was detected in the single particles from DKA. In addition Raman mapping indicated that the presence of lysozyme seemed to favor the appearance of α-mannitol in the particles from DKA evidenced by close proximity of lysozyme and mannitol in the particles.
CONCLUSIONS: It suggested that the presence of lysozyme tend to induce metastable solid state forms upon the drying process.
Original language | English |
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Journal | Pharmaceutical Research |
Volume | 32 |
Issue number | 6 |
Pages (from-to) | 1993-2002 |
Number of pages | 10 |
ISSN | 0724-8741 |
DOIs | |
Publication status | Published - 2015 |