Enhancing Stability of Exenatide-Containing Pressurized Metered-Dose Inhaler Via Reverse Microemulsion System
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The dispersibility and stability issues of peptide drugs during preparation and storage hinder the widespread adoption of pressurized metered-dose inhaler (pMDI). This study aimed to develop a reverse microemulsion (RM) of exenatide (EXE) pMDI through a liquid-based bottom-up method, thus to overcome the stability issue of peptide drugs encountered in traditional top-down methods, such as milling down and high-pressure homogenization. In this study, Pluronic® L64 (L64) was chosen as a surfactant to prepare the EXE-RM pMDI formulations with the assistance of ethanol. The results showed RM possessed a particle size of 123.80 ± 2.91 nm with 0.121 ± 0.024 PdI and a satisfied fine-particle fraction of 41.30 ± 3.73% measured by a next-generation impactor. In addition, the dispersion stability of RM pMDI was maintained after storage at 4 °C for 50 days. The secondary structure of EXE was maintained during the preparation process. Moreover, the results indicated that L64 was compatible with cells and could improve the penetration of EXE through cell monolayers. Through the liquid-based bottom-up method, EXE-RM pMDI was successfully prepared and exhibited favorable stability and aerodynamic performance. This study offers a preparation strategy to enhance the stability of peptides in pMDIs.
KEY WORDSpulmonary drug delivery system pressurized metered-dose inhaler peptide drugs reverse microemulsion non-ionic surfactants
This work was supported by the National Science Foundation of China Grants 81202476 and 81673375, the Basic Scientific Research Business Expense of the University for the Young Teacher Cultivation Project of Sun Yat-Sen University (Grant No. 16ykpy23), and the 111 project (Grant No. B16047).
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