Abstract
Background Pulmonary drug delivery route is gaining much attention because it enables to target
the active ingredients directly to lung both for local and systemic treatments, which
maximize the therapeutic effect and minimize unwanted systemic toxicity. Dry powder
inhaler (DPI) systems for asthma therapy have shown several merits to the other pulmonary
delivery systems such as nebulizers and metered dose inhalers.
Purpose The present study aims to develop and optimize a DPI formulation for Ketotifen fumarate
through spray drying technique.
Methods Particles size and morphology, crystallinity, and drug-excipient interaction of fabricated
DPI formulations were evaluated by scanning electron microscopy, X-ray diffraction
(XRD), differential scanning calorimetry (DSC), and Fourier Transform Infrared Spectroscopy
methods, respectively. The aerosolization indexes and aerodynamic properties of dry
powders were determined by next generation impactor. The powder flowability was assessed
by measuring the Hausner ratio and compressibility index.
Results Among solvent systems, ethanol-water mixture produced the most desirable powder property
for inhalation after spray drying. Although co-spray dried formulations with ammonium
bicarbonate resulted in the porous structure, it was not beneficial for DPI formulations
due to the interaction with Ketotifen. DSC and XRD experiments proved the amorphous
structure of prepared powders, which were stable for 12 months.
Conclusion The results of this study demonstrate the potential of Ketotifen DPI formulation
and pave a way to use it easily in an industrial scale.
Key words
Dry powder inhaler - DPI - Ketotifen - Pulmonary drug delivery - next generation impactor
