Raman mapping of mannitol/lysozyme particles produced via spray drying and single droplet drying

TY - JOUR

T1 - Raman mapping of mannitol/lysozyme particles produced via spray drying and single droplet drying

AU - Pekka Pajander, Jari

AU - Matero, Sanni Elina

AU - Sloth, Jakob

AU - Wan, Feng

AU - Rantanen, Jukka

AU - Yang, Mingshi

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

U2 - 10.1007/s11095-014-1592-z

DO - 10.1007/s11095-014-1592-z

M3 - Journal article

C2 - 25504535

SN - 0724-8741

VL - 32

SP - 1993

EP - 2002

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 6

ER -