Spray dried amikacin powder for inhalation in cystic fibrosis patients: A quality by design approach for product construction

An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high restorability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement.