Polyamines can act as targeting moieties during drug delivery to the lungs as they are actively taken up by pulmonary artery endothelial cells and they contain charged functionalities, which provide an opportunity to form links to therapeutic agents through ion-pairing. In the present study, the ability of polyamines to form ion-pair complexes with theophylline (THE) and the physicochemical consequences of the ion-pair process was characterised. The THE-amine association Fourier Transform Infrared spectroscopy (FTIR) experiments showed that THE formed ion-pairs with all the tested polyamine counterions when the counterions were present in a molar excess. THE showed the strongest binding association with spermine at pH 9.4 in water (pKapp = 1.96) followed by spermidine (pKapp = 1.93) then ethylenediamine (pKapp = 1.43). All of the polyamines showed a stronger binding affinity with THE compared to the monoamine, ethylamine (pKapp = 1.32). The ion-pair complexes displayed a significantly (p<0.05) lower lipophilicity and increases aqueous solubility compared to the parent drug and these physicochemical effects were greater at pH 9.4 compared to pH 7.4. As the THE-spermine showed the greatest changes in physicochemical properties followed by THE-spermidine > THE-ethylenediamine > THE-ethylamine, it appeared that the number of amines in the counterion structure was critical in modifying the THE properties.