The distribution of oleic acid between salbutamol base drug and different propellant blends.

The distribution of oleic acid between Salbutamol base drug and the solvent in metered-dose inhalers (MDI's) has been investigated. The equilibrium surfactant concentration in the drug dispersions has been determined using a colorimetric method. The samples examined contained Salbutamol base drug particles and oleic acid dispersed in different propellant blends of freon 11 and 12. The maximum equilibrium concentration observed depended on the propellant blend used. The propellant blend and the distribution of the surfactant affected the dispersion stability. The effect of the surfactant is illustrated by the adsorption isotherm for oleic acid onto the Salbutamol particles. The results are correlated with zeta-potentials and particle size measurements made on similar systems in order to characterize the properties of surfactant stabilized MDI's.

Electrophoretic mobility of salbutamol drug powder in mixed propellant solvents.

The influence of lipids on the dispersion properties of micronized Salbutamol base drug in liquid fluorocarbons has been characterized by electrophoretic mobility measurements and by particle size measurements. A modified Malvern ps26 microelectrophoretic cell was employed, allowing pressurized samples to be analyzed. The measurements were carried out at 25 degrees C in 100:0, 50:50, 40:60, and 30:70 blends of trichlorofluoromethane (P11) and dichlorodifluoromethane (P12) as a function of oleic acid concentration. A limited number of measurements were also done with soybean lecithin or synthetic dipalmitoylphosphatidylcholine (DPPC). A solvent series based on the polarizability (alpha) and on the dipole moment (mu) of the solvent molecules is constructed in order to estimate the acid-base character of the propellants. The results indicate that the type and the amount of lipids and also the type of fluorocarbon mixture plays an important role in the formation of surface charge. The dispersion stability with respect to the measured particle size does not always correlate with the measured electrophoretic mobility, and hence, the surface charge cannot alone explain the dispersion stability. Instead, the wettability of the powders seems to be important as well. Positive surface charge is obtained with the oleic acid or with synthetic dipalmitoylphosphatidylcholine, but negative surface charge exists with soybean lecithin.