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Particle size dependence of polymorphism in spray-dried mannitol

2011; Elsevier BV; Volume: 44; Issue: 1-2 Linguagem: Inglês

10.1016/j.ejps.2011.06.002

1879-0720

Yan-Ying Lee, Jian Wu, Mingshi Yang, Paul M. Young, Frans van den Berg, Jukka Rantanen,

Granular flow and fluidized beds

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.