TY - JOUR
T1 - Particle size dependence of polymorphism in spray-dried mannitol
AU - Lee, Yan-Ying
AU - Wu, Jian-Xiong
AU - Yang, Mingshi
AU - Young, Paul M.
AU - van der Berg, Franciscus Winfried J
AU - Rantanen, Jukka
PY - 2011/9/18
Y1 - 2011/9/18
N2 - The purpose of this project was to investigate the polymorphic variation of spray-dried mannitol model formulations as a function of particle size. Spray-dried powders with varying mannitol polymorphs were produced by adjusting process parameters, using co-solvent and adding a model protein (lysozyme). The obtained dry powders were dispersed into different size fractions using a Next Generation Pharmaceutical Impactor. The mannitol polymorphs in the different size fractions were analyzed using X-ray powder diffraction (XRPD), Fourier transform near infrared (FT-NIR) and Raman spectroscopy. Chemometrics was applied to interpret the FT-NIR and Raman spectra. Different spray-dried mannitol systems were established in this study, which contain mixtures of α- and β-mannitol. The XRPD, FT-NIR and Raman studies showed that the use of ethanol as a co-solvent increased the amount of α-mannitol in the smaller particles. The addition of low levels of lysozyme resulted in more α-mannitol in the smaller particles, while an increased content of lysozyme in spray-dried mannitol system resulted in more β-mannitol in the smaller particle size fraction. In conclusion spray-drying of mannitol based formulations can result in variation in the solid state composition of mannitol as a function of particle size. This finding may be clinically relevant and underlines the need for proper process control of inhalable dry powder produced by spray-drying.
AB - The purpose of this project was to investigate the polymorphic variation of spray-dried mannitol model formulations as a function of particle size. Spray-dried powders with varying mannitol polymorphs were produced by adjusting process parameters, using co-solvent and adding a model protein (lysozyme). The obtained dry powders were dispersed into different size fractions using a Next Generation Pharmaceutical Impactor. The mannitol polymorphs in the different size fractions were analyzed using X-ray powder diffraction (XRPD), Fourier transform near infrared (FT-NIR) and Raman spectroscopy. Chemometrics was applied to interpret the FT-NIR and Raman spectra. Different spray-dried mannitol systems were established in this study, which contain mixtures of α- and β-mannitol. The XRPD, FT-NIR and Raman studies showed that the use of ethanol as a co-solvent increased the amount of α-mannitol in the smaller particles. The addition of low levels of lysozyme resulted in more α-mannitol in the smaller particles, while an increased content of lysozyme in spray-dried mannitol system resulted in more β-mannitol in the smaller particle size fraction. In conclusion spray-drying of mannitol based formulations can result in variation in the solid state composition of mannitol as a function of particle size. This finding may be clinically relevant and underlines the need for proper process control of inhalable dry powder produced by spray-drying.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.ejps.2011.06.002
DO - 10.1016/j.ejps.2011.06.002
M3 - Journal article
C2 - 21699976
SN - 0928-0987
VL - 44
SP - 41
EP - 48
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
IS - 1-2
ER -