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The motive behind present work was to discover a solution for overcoming the problems allied with a deprived oral bioavailability of salbutamol sulfate (SS) due to its first pass hepatic metabolism, shorter half-life, and systemic toxicity at high doses. Pulmonary delivery provides an alternative route of administration to avoid hepatic metabolism of SS, moreover facilitated diffusion and prolonged retention can be achieved by incorporation into liposomes. Liposomes were prepared by thin film hydration technique using 32 full factorial design and formulation was optimized based on the vesicle size and percent drug entrapment (PDE) of liposomes. Optimized liposomal formulation exhibited an average size of about 167.2 ± 0.170 nm, with 80.68 ± 0.74% drug entrapment, and 9.74 ± 1.10 mV zeta potential. The liposomal dispersion was then spray dried and further characterized for in-vitro aerosol performance using Andersen Cascade Impactor. Optimized liposomal formulation revealed prolonged in-vitro drug release of more than 90% up to 14 h following Higuchi's controlled release model. Thus, the proposed new-fangled liposomal formulation would be a propitious alternative to conventional therapy for efficient and methodical treatment of asthma and alike respiratory ailments. [ABSTRACT FROM AUTHOR]