Rw. Niven et al., PROTEIN NEBULIZATION .2. STABILIZATION OF G-CSF TO AIR-JET NEBULIZATION AND THE ROLE OF PROTECTANTS, International journal of pharmaceutics, 127(2), 1996, pp. 191-201
Air-jet nebulization induces aggregation and degradation of granulocyt
e-colony stimulating factor (G-CSF). The air-water interface as a site
for destabilization of G-CSF is investigated and possible mechanisms
of stabilization by polyethylene glycol (PEG) and Tween 80 are propose
d. Equilibrium surface tension measurements show that G-CSF is highly
surface-active, but dynamic surface tension measurements made using a
maximum bubble pressure surface tensionometer show that G-CSF and surf
actants have little surface activity in the interval between formation
and destruction of aerosol generated within a nebulizer. Bubbling of
air through solutions of 4 mg/ml G-CSF for up to 1 h resulted in appro
ximate to 10% aggregation of total protein suggesting that destabiliza
tion at the air-water interface occurs. Polyethylene glycol (PEG) and
Tween 80 are effective in reducing aggregation and degradation of G-CS
F but their respective modes of protection differ. Protection is impro
ved by increasing the PEG molecular weight and concentration indicatin
g that PEG may influence stability through steric effects. In contrast
, the protective effects of Tween 80 appear to relate tp the micellar
properties and not to the surface activity of the surfactant.