Lecithin inverse microemulsions for the pulmonary delivery of polar compounds utilizing dimethylether and propane as propellants

Abstract

Lecithin inverse microemulsions were investigated as a means of pulmonary drug delivery utilizing dimethylethyleneglycol (DMEG) and hexane as models for dimethyl ether (DME) and propane, respectively, Addition of lecithin to the model propellant mixtures increased the solubility of water in a nonlinear, solvent-dependent manner. The concentration of water necessary to fully hydrate cobalt(ll) decreased as the solvent composition was varied from DMEG to hexane. Water proton chemical shift decreased in the presence of lecithin, with the largest increases in high hexane content samples. Equilibrium analysis and component diffusion rate determination (by pulsed-field gradient [PFG]-NMR) indicated the quality of water associated with the dispersed phase. Collectively, these methods demonstrated that a greater function of water was associated with the microemulsion-dispersed phase as the solvent was varied from DMEG to hexane. Iodine solubilization indicated microemulsion formation (operational critical micelle concentration [cmc] 10 moles water per mole lecithin) at similar to 10(-4)-10(-5) molal lecithin. NMR data (trimethylammonium proton chemical shift, water and lecithin TI) were consistent with microemulsion formation. Water-soluble compounds dissolved in lecithin inverse microemulsions in a lecithin- and water-dependent manner Experiments with DME/lecithin demonstrated microemulsion characteristics similar to those in the model propellant. DME/lecithin metered-dose inhalers (MDIs) produced a particle size and a fine particle fraction (36% by twin inpinger method) suitable Sor pulmonary drug delivery