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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(04): e275-e283
DOI: 10.1055/s-0042-1758388
Original Article

The Study of Spray-Freeze-Drying Technique for Development of Novel Combination pMDIs, Part II: In Vitro and In Vivo Evaluations

Quan Xi
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
,
Jia-Ying Miao
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, 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

The mometasone furoate (MF) and formoterol fumarate dihydrate (FF) inhalable microparticles prepared by different methods, such as micronized active pharmaceutical ingredients (APIs), microparticles of APIs prepared by spray-freeze drying technique (SFD APIs), and phospholipid microparticles of APIs prepared by SFD (SFD Lip-APIs), showed different inhaled drug delivery characteristics. Study on the physicochemical characteristics of those microparticles and the effect of matrix excipients on pharmacokinetic (PK) behaviors of inhalable microparticles is helpful for the development of new methods for inhalable microparticles with excellent performance of inhalation characteristics. In this study, the crystal state of the microparticles was investigated by powder X-ray diffraction and differential scanning calorimetry. The density was investigated by a bulk density method. The suspension and dispersion characteristics were determined by observing its state in hydrofluoroalkane (HFA). Meanwhile, the PK behaviors of SFD Lip-APIs in beagle dogs were also investigated by airway administration to evaluate the effect of phospholipids on drug release. The results indicated that the presence of phospholipids prevents the formation of solid bridges bonding to each other during SFD of pure drug solutions. In comparison to the conventional micronized microparticles, inhalable drug–phospholipid microparticles were easily dispersed and suspended in HFA. The embedded drugs were in a crystal state that endowed a better physical stability, and most interestingly, have similar PK behavior to the control (a mixed solution of MF/FF), suggesting that the phospholipids, as matrix excipients, had no effect on absorption. Given above, our designed SFD phospholipid microparticles may represent an efficient carrier for pulmonary delivery of MF and FF for further clinical treatment.

Keywords

inhalable microparticles - spray-freeze-drying - characterization - airway administration - pharmacokinetic


Publication History

Article published online:
27 December 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/)

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