Formulation and evaluation of fluticasone propionate microemulsions for nebuliser devices

Precious Akhuemokhan, Mark Parry, Mireille Hassoun, Mark Hammond, Ben Forbes

Purpose: To formulate fluticasone propionate (FP) microemulsions (ME) for pulmonary delivery using jet or vibrating mesh nebulisers, characterise the MEs by determining their physicochemical properties and compare their performance against the licensed FP nebuliser suspension (Flixotide® nebules).
Method: The formulations were based on microemulsion formulations licensed for non-pulmonary routes of administration. Three microemulsions (ME1, ME2 and ME3) were prepared and their viscosity and density measured. The aerosolisation performance of microemulsions and Flixotide® was assessed by measuring delivery rate and respirable dose according to the European Pharmacopoeia guidelines. Aerosol particle size distribution was measured by laser diffraction and the aerodynamic size profile was determined by fractionation using a next generation impactor (NGI).
Results: The mesh nebuliser failed to aerosolise any of the microemulsions, whereas the jet nebuliser was effective at delivering ME1, ME2 and Flixotide. The microemulsions had varying viscosities (ME1; 2.64 cP, ME2; 7.74 cP, ME3; 107.00 cP). ME1 and Flixotide had similar delivery rates, but delivered different doses (ME1 27.07%; Flixotide 52.48%). ME2 exhibited the lowest delivery rate and delivered dose. In terms of particle size and aerodynamic particle size distribution, ME2 had the lowest volume diameter for 90% of droplet population (Dv(90)), highest fine particle dose (FPD) and lowest mean mass aerodynamic diameter (MMAD). For ME1, ME2 and Flixotide, respectively, Dv(90) = 8.71 μm, 7.09 μm, 8.51 μm, FPD= 73.23%, 79.55%, 73.96% and MMAD= 4.60 μm, 4.18 μm, 4.95 μm.
Conclusion: In this study, the ME showed no major improvement over Flixotide. However, the aerodynamic particle size distributions produced by ME1 and ME2 using a jet nebuliser showed these to be promising prototype formulations, which also have the potential to offer clinical advantages or novel formulation options for the next generation of nebulisers, e.g. small volume devices.

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