Dynamics and distribution of aromatic model drugs in the phase transition of thermoreversible poly(N-isopropylacrylamide) in solution

Employing differently substituted benzaldehydes as model drugs, their dynamics is investigated under the influence of the coil-to-globule transition of poly(N-isopropylacrylamide), which shows lower critical solution temperature behaviour. Using ¹H-NMR spectra, partial incorporation of the model drug into precipitated polymer particles is shown. The fraction of drug, which is rigidly incorporated, is linearly correlated to the shift of the transition temperature, which it induces for the polymer. By ¹H-NMR spin relaxation measurements on ethylvanillin, 3,4-dimethoxybenzaldehyde and salicylaldehyde the influence of the polymer transition on the model drug dynamics is detected. The data are interpreted in terms of different sites of drug localisation, i.e. rigidly incorporated, loosely bound and free in the aqueous phase, which are identified by their different dynamics. Drug molecules strongly interacting with the polymer, as documented by a large shift of the transition temperature, exhibit only strongly bound and free sites, while with decreasing drug–polymer interaction drug an additional loosely bound site occurs.