Formulation and evaluation of albuterol metered dose inhalers containing tetrafluoroethane (P134a), a non-CFC propellant.

This study was undertaken to evaluate tetrafluoroethane (P134a) as a possible chlorofluorocarbon (CFC) replacement for albuterol metered dose inhaler (MDI) formulations. Preformulation studies using three conventional (oleic acid, sorbitan trioleate, lecithin) and a nonconventional (oleyl alcohol) surfactant indicated that P134a is a poor solvent for these surfactants. A slight improvement in the solubility of oleic acid and oleyl alcohol was observed by the addition of low concentrations of a nonconventional cosolvent diethyl ether (< or = 0.5% w/w). Formulation screening of the prepared albuterol formulations indicated that suspensions containing oleyl alcohol and diethyl ether had a slower rate of separation. Product performance of four albuterol formulations containing oleyl alcohol, diethyl ether, and P134a was evaluated and compared to a leading commercial formulation containing CFC propellants (Ventolin). Ventolin showed excellent agreement between the emitted dose and the expected dose but only a reasonable agreement was observed with one of the better P134a-containing formulations. P134a formulations showed higher internal pressure in comparison to the CFC formulation. The concentrations of the surfactant, drug, and cosolvent appeared to have a significant impact on the uniformity of the emitted dose. Determination of particle size using the time-of-flight and the laser diffraction analyzer revealed that P134a formulations had equal or smaller particle size than the formulation containing CFC. However, the CFC formulation showed a higher respirable fraction than the P134a formulation when measured by the two inertial impaction methods. The observed particle size distribution of the formulation appeared to depend on the measuring method used.

Compatibility evaluation of metered-dose inhaler valve elastomers with tetrafluoroethane (P134a), a non-CFC propellant.

Compatibility of propellants, excipients, and solvents with the components of the valve greatly influences performance of metered-dose inhalers (MDIs). Ozone-friendly hydrofluoroalkane propellant 134a has potential for use as a chlorofluorocarbon (CFC) replacement. No suitable replacement for propellant 11 and 114 has yet been found and the problems arising from this may be overcome by use of ethanol as a solvent. In this study, compatibility of MDI valve elastomers Dowty Nitrile 0117, White Buna, and Type 674 (B) with P134a placebo formulations having different concentrations of ethanol was investigated. The results indicate that formulations containing no ethanol adversely affected the functioning of the valves. Higher concentrations of ethanol improved valve performance, but showed increased leakage. Physical characteristics of the valve elastomers evaluated by determining swelling caused after exposure to the P134a placebo formulations exhibited increased swelling with increasing concentrations of ethanol in the formulation.