Abstract: In order to minimize the residual tert-butyl alcohol (TBA) level in cyclodextrin complex prepared by freeze drying TBA/water cosolvent system, the formulation and lyophilization procedure that may influence the residual TBA was studied. Residual TBA in freeze dried cyclodextrin complex was determined by gas chromatography. The significant formulation and processing factors that influence residual TBA were identified by adjusting the initial TBA concentration in cosolvent, selecting cyclodextrin type (β-cyclodextrin or hydroxypropyl β-cyclodextrin), changing sample volume in flasket, altering freezing mode (fast freezing or slow freezing) and modifying the duration of secondary drying. The results show that the amorphous cyclodextrin material (hydroxypropyl β-cyclodextrin), initial low TBA concentration in cosolvent and fast freezing would lead to high TBA residue in cyclodextrin complex, annealing was effective in reducing the residual TBA. The duration of secondary drying had no distinct effect on residual TBA. It is concluded that in order to reduce residual TBA in cyclodextrin complex prepared by lyophilization monophase solution, the initial TBA concentration in cosolvent should be higher than the crystal formation concentration, the appropriate cyclodextrin type and freeze drying processing should be choosen.