OBJECTIVES: To investigate the effects of formulation composition on the physico-chemical and drug release properties of mucoadhesive buccal films prepared by melt extrusion technology, using a response surface methodology. METHODS: Salbutamol sulphate, an antiasthmatic drug was used for this study. Klucel hydroxypropylcellulose (HPC) EF (film-forming polymer), Benecel hydroxypropylmethylcellulose (HPMC) K-15M (drug release retardant) and polyethylene glycol (PEG) 4500 (plasticiser) were the three independent factors utilised for the study. The responses were fitted to a full quadratic model and P-values for each of the factors were used to determine their significance on the film characteristics. KEY FINDINGS: Films were successfully extruded using the corotating twin-screw extruder. The torque during extrusion was found to be significantly affected by all the three factors and no interaction between factors was observed. A significant interaction was observed between HPC and PEG 4500 for stiffness of films. For disintegration time and swelling index, a significant interaction was found between HPC and HPMC. The in vitro % drug release was directly correlated with HPMC content and not with other factors and varied from 69-89% at 4 h. CONCLUSIONS: The influence of extrusion process and formulation parameters on salbutamol sulphate films was elucidated, indicating the use of melt extrusion as a feasible method for film preparation.