Formulation and in vitro evaluation of pressurized inhalation aerosols containing isotropic systems of lecithin and water

Abstract

Reverse micellization of nonionic surfactants in apolar media was applied to the formation of solution phase, pressurized inhalation aerosols, employing soya lecithin (SPC) and water in chlorofluorocarbon (CFC) blends. The use of a 30/70 mixture of trichlorofluoromethane (P11) and dichlorodifluoromethane (P12) resulted in the formation of stable, isotropic systems containing 0.5-2.0% (w/v) SPC and solubilized water; R (moles water/moles SPC), 0.9 to 4.28. In systems containing less than 30% P11, phase separation became apparent, particularly at higher water and surfactant concentrations. Dramatic changes in solution viscosity were noted on increasing R values and were attributed to an increase in asymmetry of SPC micelles. Dynamic fractionation of the output from pressurized aerosols using a four-stage liquid impinger showed that the respirable fraction (as measured by the percentage of emitted droplets with aerodynamic diameters less than 5.5 microns) was highly dependent on SPC concentration and R. A significant correlation between RF and actuator score, based on orifice diameter and length, was also found and confirmed that the highest RF values were achieved with the systems of lowest SPC and water concentrations sprayed through an actuator with the smallest and shortest orifice dimensions. This novel mechanism for the formulation of hydrophilic drugs as solutions within CFC-based pressurized aerosols may offer advantages over the traditional suspension approach to pulmonary drug delivery.