Solid State Interaction study on the system polyvinylpyrrolidone-XL/trimethoprim

Abstract

The interaction between cross-linked polyvinylpyrrolidone (PVP-XL) and trimethoprim (TMP) has been studied by Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Photoacoustic Spectroscopy (FTIR/PAS). DSC measurements show that very different thermal traces are obtained on ground and not-ground mixtures suggesting that some type of interaction takes place in the first ones. SEM analysis however shows that TMP particles of much smaller dimension than expected can be easily found inside polymer cavities in not-ground mixtures, indicating that an interaction takes place in these mixtures too, leading to drug particles fragmentation and ingestion by polymer cavities. FTIR/PAS measurements give very similar spectra for both types of mixtures thus showing that basically the same interaction phenomena take place independent on whether mixtures were or were not co-ground. Spectra analysis leads to the conclusion that hydrogen bonds are responsible for component interaction and that polymer-adsorbed water plays an important role in the process. Taking into account the polymer water content, an interaction model is proposed by which a mixture composition of maximum interaction can be calculated which is in good agreement with that obtained, on a purely phenomenological basis, by DSC measurements. The surprisingly different thermal behaviours of ground and not-ground mixtures, and particularly the fact that TMP apparently fails to melt in the first ones, are explained on the basis of the very small cluster sizes obtained, in the ground mixtures, as a consequence of the combined effects of component interaction and co-grinding.