Influence of stabilizers on the physicochemical characteristics of inhaled insulin powders produced by supercritical antisolvent process.
OBJECTIVE
To examine the effect of stabilizers on aerosol physicochemical characteristics of inhaled insulin particles produced using a supercritical fluid technology.


METHODS
Insulin with stabilizers such as mannitol and trehalose was micronized by aerosol solvent extraction system (ASES). The supercritically-micronized insulin particles were characterized for size, shape, aerosol behavior, crystallinity and secondary structure.


RESULTS
Experimental results indicated that when insulin was incorporated with the most commonly used stabilizer mannitol (insulin/mannitol: 15/85 wt.%, designated IM), the particles formed were irregular and needle-shaped and had a tendency to agglomerate. With the incorporation of a second stabilizer trehalose (insulin/mannitol/trehalose: 15/70/15 wt.%, designated IMT), the particles were relatively uniform, more spherical, less cohesive, and less agglomerated in an air flow, when compared to IM particles. The mass median aerodynamic diameter of the IMT particles was 2.32 mum which is suitable for use in inhalation therapy. In vitro deposition test using micro-orifice uniform deposit impactor showed 69 +/- 7 wt.% of the IMT particles was deposited in stage 3, 4, 5 and 6 while 41 +/- 15 wt.% of the IM particles was deposited in the same stages. In terms of insulin stability, secondary structures of insulin particles were not adversely affected by the ASES processing studied here.


CONCLUSIONS
When properly formulated (as in IMT particles), ASES process can produce particles with appropriate size and size distribution suitable for pulmonary insulin delivery.
Kim
Yong Ho
YH
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-1211, USA.
Sioutas
Constantinos
C
Shing
Katherine S
KS