Pain is one of the most prevalent and difficult to manage symptoms in cancer patients, and
conventional drugs present a range of adverse reactions. The development of -cyclodextrins (-CD)
complexes has been used to avoid physicochemical and pharmacological limitations due to the
lipophilicity of compounds such as p-Cymene (PC), a monoterpene with antinociceptive effects. Our
aim was to obtain, characterize, and measure the effect of the complex of p-cymene and -cyclodextrin
(PC/-CD) in a cancer pain model. Initially, molecular docking was performed to predict the viability
of complex formation. Afterward, PC/-CD was obtained by slurry complexation, characterized
by HPLC and NMR. Finally, PC/-CD was tested in a Sarcoma 180 (S180)-induced pain model.
Molecular docking indicated that the occurrence of interaction between PC and -CD is favorable.
PC/-CD showed complexation efficiency of 82.61%, and NMR demonstrated PC complexation
in the -CD cavity. In the S180 cancer pain model, PC/-CD significantly reduced the mechanical
hyperalgesia, spontaneous nociception, and nociception induced by non-noxious palpation at the
doses tested (p < 0.05) when compared to vehicle differently from free PC (p > 0.05). Therefore, the
complexation of PC in -CD was shown to improve the pharmacological effect of the drug as well as
reducing the required dose.