11
high final product yields (96%) for the preparation of budesonide and indomethacinHPBCD
complexes. Zijlstra, et. al. (2004) showed that it is possible for a stable peptide to be micronized with
milling, spray drying and spray freeze drying without degradation of the drug. Whether a micronization
technique produces particles that are suitable for use in an inhalation formulation was found to depend on
the type of formulation and formulation process used. Furthermore, the performance of the different
formulations (aerosolization behaviour expressed as fine particle fraction) was found to depend on the
efficiency of the de-agglomeration principle applied. Such an inhalation system could be further
developed to be a non-invasive alternative for routine administration of cetrorelix.
Different drugs had been tested using different micronization methods; with different stabilization agent
and solvent. The ultimate target is to obtain the optimum operating conditions with reasonable economic
prospect for the micronization technologies.
REFERENCES
Bandi, N., William, W., Christopher, B. R., Kotra, L.P., and Kompella, U.B. 2004. "Preparation of
budesonide and indomethacinhydroxypropyl-
-cyclodextrin (HPBCD) complexes using a single-
step, organic-solvent-free supercritical fluid process". European Journal of Pharmaceutical
Sciences. vol. 23 pp.159168.
Berggren, J, Frenning, G. and Alderborn, G. 2004. "Compression behaviour and tablet-forming ability of
spray-dried amorphous composite particles" European Journal of Pharmaceutical Sciences vol. 22 ,
pp.191200
JetPharma SA Jetmill product brochure.
Krummer, K. and Ong, S.L. 2001. "Micronizer" Thesis for the Joint Masters Program between NUS and
UIUC, Unpublished.
Lizio, R., et al. 2001. "Low Temperature Micronization of a Peptide Drug in Fluid Propellant: Case Study
Cetrorelix".
AAPS PharmaSciTech. 2(3) article 12. [On-line]. Available from:
http://www.aapspharmscitech.org/articles/pt0203/pt020312/pt020312.pdf
[Accessed 12 March
2005].
Müller, B.W. and Rasenack, N. 2004. "Micron-Size Drug Particles: Common and Novel Micronization
Techniques". Pharmaceutical Development and Technology. Vol. 9, No. 1, pp. 1-13.
Zijlstra, G.S., Hinrichs, W.L.J, A.H. de Boer, and Frijlink, H.W. 2004. "The role of particle engineering
in relation to formulation and de-agglomeration principle in the development of a dry powder
formulation for inhalation of cetrorelix". European Journal of Pharmaceutical Sciences. Vol. 23,
pp.139149.
