Enhancing Stability of Exenatide-Containing Pressurized Metered-Dose Inhaler Via Reverse Microemulsion System

Abstract

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.

Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals

“…If inhaled insulin becomes successful for diabetic therapy in terms of bioavailability and treatment cost, it will most probably create opportunities for the use of other biopharmaceuticals as inhalation preparations. Recently, other proteins and peptides have been studied for treating diabetes through the pulmonary route [ 100 , 102 ]. The major concerns regarding the long-term application of protein inhalers, such as insulin, are the development of insulin-antibodies and lung safety issues, which should be considered in future studies.…”

A Pilot Study Exploiting the Industrialization Potential of Solid Lipid Nanoparticle-Based Metered-Dose Inhalers

“…The filling process of MDI had been reported elsewhere [ 18 ], and the content of components could be referred to the literature [ 17 ]. Pluronic L64, ethanol, and SLN (SLN(0), SLN(+) and SLN(−)) were added successively into the aerosol container, which was sealed by a 50-μL metered-dose valve.…”

Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices

“…For better consolidation of incretins' analytical quantification through ELISA, Table 2 briefly displays ELISA settings and protocol conditions for biological matrices and API formulation matrices [[43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54]].…”