Inhalable Glucagon-like Peptide 1 Porous Particles Prepared by Spray Freeze Drying Technique

Sanketkumar Pandya, Amit Misra

Background: Glucagon-like peptide 1 (GLP-1) is an incretin hormone with multi-faceted actions that find use in the management of type 2 diabetes mellitus. This study focuses on the development and characterization of a GLP-1 loaded dry powder inhalation (DPI) formulation prepared by spray-freeze drying (SFD) technique. Methods: Inhalable porous GLP-1 particles were prepared by SFD, using a blend of L-leucine and trehalose, and the particles were characterized in terms of particle size distribution and morphology. Carr’s index (CI) and angle of repose (θ), which are measures of powder flow properties, were calculated. In-vitro aerosol performance was assessed in terms of mass median aerodynamic diameter (MMAD), fine particle fraction (FPF) and geometric standard deviation (GSD) using Andersen Cascade Impaction (ACI). The specific surface area (SSBET) of porous particles was determined by nitrogen adsorption-desorption method. The viability of A549 (lung adenocarcinoma) cells after exposure to the DPI was assayed to evaluate the toxic effects of the DPI formulation on alveolar epithelial cells. Results: Particles prepared in high yield (~90%) by SFD exhibited good dispersibility and aerodynamic performance (MMAD=3.7±0.01 μm, FPF=60.5±0.5%). Particles showed good flow properties but poor compressibility. Scanning electron microscopy (SEM) revealed that particles were highly porous structures, and possessed high SSBET (5.676 m2/g) and low density (0.03 g/ml). In-vitro cytotoxicity studies on A549 cells indicated that the particles did not exert significant cytotoxicity. Conclusion: A suitable inhalable formulation of GLP-1 was developed that may be used for the treatment of type 2 diabetes mellitus.

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