The effect of hydroxypropyl methylcellulose (HPMC) on complexation of praziquantel with beta cyclodextrin (PRZ–βCD) in solution and in the solid state was investigated. Phase solubility studies of βCD (0, 3, 6, 9 and 12 mmol L−1) were carried out by adding an excess amount of PRZ (8 mmol L−1) in the absence and presence of the polymer (with and without heating at 120 °C). Equimolar binary and ternary complexes were prepared by kneading and freeze-drying and characterized by DSC, DTA TGA, FTIR, XRPD and SEM patterns. A stoichiometry ratio of 1:1 was indicated by phase-solubility studies both in the presence and absence of 0.5 % HPMC. The molecular modeling confirms the 1:1 stoichiometry rate with Higuchi’s Al type. The presence of HPMC improved the complexation between PRZ and βCD by increases in both the intrinsic solubility of the drug as well as in values of the stability constant, complexation efficiency and Gibb’s free energy of the complex, principally in the presence of heating (up to ninefold relative to aqueous solubility of the drug). The synergic effect of HPMC was also observed in thermal analysis, with lower dehydration enthalpy for ternary complexes. The results of melting enthalpy were according to XRPD results, indicating that the preparation technique and presence of HPMC influenced thermal and crystallographic characteristics of inclusion complexes. The FTIR patterns suggest the complexation mechanism while SEM patterns showed the formation of inclusion complexes. The use of the HPMC and freeze-drying technique suggest more effective formation of PRZ:βCD inclusion complexes.