Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

Abstract

Water soluble compounds were incorporated into metered-dose inhalers (MDIs) by using water-in-propellant lecithin microemulsions, in which dimethyl ether (DME) and propane acted as both continuous phase and propellant. Lecithin, water, and water soluble compounds were added to glass MDI containers, valves were crimped on, and propellants were added using a pressure burette. Aerosols were produced using commercially available actuators, and inertial impaction was used to determine the mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF) of the resulting aerosols. The DME/propane/lecithin microemulsion MDIs generated aerosols with particle size distributions suitable for pulmonary delivery (eg, MMAD 3.1 µm, FPF 59% for DME with lecithin content 3%, water content 2.5% [wt/wt]). Increasing water concentration (up to 8% wt/wt) was correlated with a reduction in FPF. Freezing and rewarming had no adverse effect on MMAD, GSD, or FPF. Storage of microemulsion samples for up to 3 weeks did not adversely affect the MMAD, GSD, or FPF. This approach may enable the pulmonary delivery of water soluble therapeutic agents via MDIs.

Advances in Metered Dose Inhaler Technology: Formulation Development

“…Additionally, the half-life of these HFA propellants in the atmosphere is a fraction of that of the CFCs they replaced (3). Other propellants have been explored as replacements for CFCs, namely, 1,1-difluoroethane (HFA 152a), propane, n-butane, isobutane, n-pentane, isopentane, neopentane, dimethylether, and hydrofluoro-olefins (HFO) (18)(19)(20)(21)(22)(23)(24). Many of these propellants have not been extensively studied and toxicological risks have not been assessed because they are flammable and thus pose an inherent safety risk.…”

Development of Budesonide Microparticles Using Spray-Drying Technology for Pulmonary Administration: Design, Characterization, In Vitro Evaluation, and In Vivo Efficacy Study

“…Particle size and potential toxicity of excipients are critical factors that limit the use of microparticles for pulmonary administration. The deepest penetration of particles into airways and their deposition in peripheral regions are achieved when the particle size ranges between 1 and 5 µm (7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Excipients must be physiologically acceptable, biodegradable, and nonimmunogenic and might not induce inflammatory and alloreactive responses (18).…”

Optimization and Solubilization Study of Nanoemulsion Budesonide and Constructing Pseudoternary Phase Diagram

“…Although authors have suggested using nanoemulsion formulations for inflammation [2][3][4][5][6][7]. Budesonide (16,17-butylidenebis(oxy)-11,21-dihydroxypregna-1,4diene-3,20-dione) is a synthetic glucocorticoid steroid used in the treatment of asthma and an inflammatory bowel disease [9]. Molecular weight of budesonide is 430.5, log p values are 3.2, biopharmaceutical classification system Class II and practically insoluble in water (28 µg/mL) [10].…”