Characterisation of salmon calcitonin in spray-dried powder for inhalation: Effect of chitosan - Spray Drying

Characterisation of salmon calcitonin in spray-dried powder for inhalation: Effect of chitosan
Received 19 July 2006; revised 16 October 2006; accepted 18 October 2006. Available online 27 October 2006.
M. Yanga, , , S. Velagab, H. Yamamotoc, H. Takeuchic, Y. Kawashimad, L. Hovgaarda, M. van de Weerta and S. Frokjaera
International Journal of Pharmaceutics
Article in Press
ScienceDirect
Copyright ? 2006 Published by Elsevier B.V.
aDepartment of Pharmaceutics and Analytical Chemistry, Danish University of Pharmaceutical Sciences, 2100 Copenhagen, Denmark
bDepartment of Health Sciences, Lule? University of Technology, 961 36 Boden, Sweden
cLaboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Japan
dSchool of Pharmacy, Aichi Gakuin University, Japan
Abstract
Salmon calcitonin (sCT) powders suitable for inhalation, containing chitosan and mannitol as absorption enhancer and protection agent, respectively, were prepared using a spray-drying process. The effect of chitosan on physicochemical stability of sCT in the dry powder was investigated by different analytical techniques. High-performance liquid chromatography (HPLC) analysis indicated that sCT was chemically stable upon spray-drying. With the proportion of chitosan in spray-drying formulation being increased, dissolution of sCT from the dry powders was decreased both in phosphate buffer and acetate buffer. The thioflavine T fluorescence assay showed that no fibrils were present in the spray-dried powder. However, sCT partly fibrillated in the phosphate buffer, but not in acetate buffer. Fourier transform infrared (FTIR) spectra showed that the secondary structure of sCT was slightly changed in the dry powder, yet no aggregate signal was observed. Circular dichroism analysis indicated that the structure of sCT in an aqueous formulation was slightly altered by addition of chitosan. Nevertheless, recovery of sCT was not influenced by chitosan in the aqueous formulation as indicated by HPLC analysis. This study suggested that sCT, in absence of any additives, was stable during the spray-drying process under certain conditions. Addition of chitosan affects recovery of sCT from spray-dried powders, which may be due to formation of a partially irreversible complex between the protein and chitosan during the spray-drying process.
Keywords: Salmon calcitonin; Spray-drying; Chitosan; Physicochemical characterization

Corresponding author. Present address: Novo Nordisk A/S, B6.2.030 Novo Nordisk Park, 2760 Maaloev, Denmark. Tel.: +45 44 43 69 62; fax: +45 44 43 40 28.
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