Objectives: To design a formulation and develop ODTs of AMB hydrochloride and salbutamol sulphate in combination for the treatment of respiratory disorders and perform an in vitro evaluation using superdisintegrants in combination with a suitable binder and excipients. Direct compression was used to prepare the tablets. Materials and Methods: In the present research work, different concentrations of SSG as a superdisintegrant were used to optimize the concentration of SSG in the formulation of ODTs. Different concentrations of MCC and PVP K-30 were also studied along with the optimized SSG concentration. The tablets were evaluated for hardness, friability, weight variation, wetting time, in vitro DT, and percentage drug content uniformity. The optimized formulation was further evaluated in an in vitro release study, and drug-excipient compatibility and accelerated stability study. Results: The optimized concentration of SSG was found as 4% on the basis of the lowest DT. The 1% concentration of MCC was selected as the optimum binder concentration on the basis of the lowest DT. ODTs passed all the quality control tests viz., weight variation, hardness, friability, in vitro DT, drug content (%) and wetting time. The formulation satisfied the requirements of the FDA for rapid-dissolving tablets and allowed more than 85% drug to be released within 30 min. The fourier transform infrared spectroscopy study revealed that there was no interaction between the drug and excipients. The accelerated stability study shows that formulation is quite stable at normal temperature and humidity conditions as well as at extreme temperature conditions. Conclusion: By adopting a systematic formulation approach, ODTs of AMB hydrochloride and salbutamol sulphate in fixed-dose combination can be formulated using superdisintegrants in combination with appropriate binder and excipients; this was found to be economical and industrially feasible.