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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(03): e179-e187
DOI: 10.1055/s-0042-1755455
Original Article

The Study of Spray-Freeze-Drying Technique for Development of Novel Combination pMDIs, Part I: Study on the Preparation Method

Quan Xi
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jia-Ying Miao
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Zhen Cao
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   School of Engineering, China Pharmaceutical University, Nanjing, People's Republic of China
,
Hao Wang
3   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
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Abstract

Clinically available pressurized metered-dose inhalers (pMDIs) mainly directly use micronized drugs as inhalable microparticles. Although technology for preparing pMDIs has proven to obtain clinically appropriate aerosol performance, the fine particle fraction and delivered dose content uniformity (DDCU) of pMDIs still need to be improved. DDCU problem is usually exacerbated by patients' handling errors prior to taking a dose. In this study, novel phospholipid microparticle inhalation pMDIs were prepared by a spray-freeze-drying process using mometasone furoate and formoterol fumarate dihydrate as model drugs and distearoylphosphatidylcholine as an excipient. Combined with the material composition, the atomization and freeze-drying processes were also studied. Our data showed that both atomization parameters of gas–liquid ratio and freeze-drying curve settings met the requirements of drug design. According to aerodynamic performance in vitro and DDCU evaluation, the performance of the phospholipid microparticle inhalation pMDI was better than that of the micronized drug microparticle pMDI. In conclusion, preparing pMDIs with particle engineering has the potential to ensure accuracy of quantification and to improve the efficiency of drug deposition in lungs in clinical practice.

Keywords

spray-freeze-drying - inhalable microparticles - pMDIs - phospholipids


Publication History

Received: 06 April 2022

Accepted: 12 July 2022

Article published online:
13 September 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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