The complexation between risperidone and hydroxypropyl-β-cyclodextrin (HP-β-CD) was studied in buffered cyclodextrin solutions with the aim to improve the aqueous solubility of the drug, which may allow the formulation of a suitable nasal preparation. The acid-base ionization constants of risperidone and its inclusion complex with HP-β-CD were determined by potentiometric titration. The solubility studies indicated the formation of soluble inclusion complex with equimolar stoichiometry at all pH values tested. The pH value had significant influence on the interaction mode between the risperidone and HP-β-CD, indicating the different affinity of neutral and monoprotonated drug form for the inclusion complex formation. Although the drug ionization has resulted in decrease of the complex stability constant, the overall risperidone solubility in cyclodextrin solution with pH value of 6.0 was the highest. These results may lead to novel pharmaceutical formulation of risperidone, suitable for nasal application.