Drug Res (Stuttg) 2020; 70(01): 26-32
DOI: 10.1055/a-0649-0814
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Development of a Carrier Free Dry Powder Inhalation Formulation of Ketotifen for Pulmonary Drug Delivery

Fariba Azari
1  Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
Saeed Ghanbarzadeh
2  Cancer Gene therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
3  Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
,
Rezvan Safdari
4  Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Shadi Yaqoubi
5  Research Center for Evidence Based Medicine and Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
,
Khosro Adibkia
6  Biotechnology Research Center and Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
Hamed Hamishehkar
4  Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 04 March 2018

accepted 23 June 2018

Publication Date:
18 September 2019 (online)

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.