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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.

Surfactant Design for the 1,1,1,2-Tetrafluoroethane−Water Interface: ab initioCalculations andin situHigh-Pressure Tensiometry

“…However, polar molecules, including water, have extremely low solubility in HFAs. It has been suggested that reverse aqueous aggregates can be potentially utilized for the solubilization and delivery of biomolecules to and through the lungs using pMDIs. ,, A large number of surfactants approved by the FDA for inhalation, oral, and intravenous routes of administration have been screened in the past (phase behavior measurements) with respect to their ability to form and stabilize reverse aggregates of water in HFAs ,,, Some limited success has been achieved with surfactants containing fluorinated moieties. − In those cases, either a very large amount of a non-FDA-approved amphiphile and cosolvent 37,38 or pressures above saturation (at ambient temperature) were required .…”

Microscopic and Thermodynamic Properties of the HFA134a−Water Interface: Atomistic Computer Simulations and Tensiometry under Pressure

“…Interfacial tension values for (propellant) HFA|W or CFC|W have not been previously reported in the literature. However, it is instructive to compare and contrast the properties of the HFA|W with that of the CFC|W interface given that the FDA-approved hydrogenated surfactants have been shown to form reverse aqueous aggregates in CFCs, but not in HFAs. − It has been shown that the work of adhesion between water and several immiscible organic liquids obeys a linear solvation free energy relationship, which can be summarized in a simple two-parameter equation: where W O | W is the work of adhesion between the organic phase and water, σ O and σ W are the surface tensions of the pure organic liquid and water, respectively, γ O | W is the interfacial tension, L w is the dimensionless Ostwald coefficient for solubility of the gaseous organic compound in water, and N C is correction parameter for the chain length. Using the described correlation, with the experimental value of σ HFA134a , N C = 0 and L w obtained from Henry's law constant database, and σ W = 71.99 mN/m, the estimated γ HFA134a | W at 298 K is 22.1 mN/m.…”

Ethoxylated copolymersurfactants for the HFA134a–water interface: interfacial activity, aggregate microstructure and biomolecule uptake

“…19,56 While the studies of longer chain alcohols could generate interesting fundamental results, such alcohols are generally not employed in pMDI formulations because of their potential toxicity. 9,20,71 Water-in-HFA134a reverse aggregates: UV-vis spectroscopy While the detection of the c.a.c. unambiguously demonstrates that EO 3 PO 43 EO 3 aggregates in HFA134a in the presence of water, these results do not provide any information on the microstructure of the aggregates nor on the location of the water molecules, which could be either solvating the chains that form the aggregates or in an aqueous core (microemulsion).…”