The densities of three pharmacologically significantly used drugs i.e., Chloroquine phosphate (CP), Acefylline piperazine (AP) and Gentamicin sulfate (GS) have been carried out in aqueous (aq), aqueous polyethylene glycol (aq-PEG) and aqueous polyvinyl pyrrolidone (aq-PVP) solvent systems within concentration range (0.02–0.1 ± 0.001 mol.dm−3) at different temperatures (293.15–318.15 K) with the interval of 5 K. Density data were used to evaluate volumetric properties of drugs (CP, AP and GS) by apparent molar volume, partial molar volumes, molar expansibilities and isothermal expansion coefficient. ϕE° provides information about the absence or presence of a caging or packing effect. Partial molar transfer volume was also calculated to study the hydrophilic/hydrophobic interactions in aq-PEG and aq-PVP solvent systems. The results are interpreted in terms of drug–solvent and drug-drug interactions and structure making or breaking abilities of drugs in aq, aq-PEG and aq-PVP solvent systems.