Terahertz-spectroscopy for non-destructive determination of crystallinity of L-tartaric acid in smartFilms® and tablets made from paper.

Newly developed active pharmaceutical ingredients (API) often experience low solubility in aqueous media and thus possess poor oral bioavailability. The SmartFilm®-technology is a novel approach to overcome poor solubility. The technique uses commercial paper in which API can be loaded in amorphous state, thus increasing dissolution rate dc/dt and solubility c when compared to bulk material. However, the preservation of the amorphous state is a prerequisite for an efficient use of the smartFilm-technology and thus the crystalline state needs to be inspected during storage. Preferably, this should be done non-destructively. Traditional techniques, such as x-ray diffraction (XRD) or differential scanning calorimetry (DSC), do not allow for non-destructive crystallinity investigations, whereas Terahertz (THz) spectroscopy is a non-destructive technique, that is sensitive to the crystalline state of many molecular crystals. Therefore, the potential of THz-spectroscopy for crystallinity state inspection of API in smartFilms and tablets made from smartFilms was investigated in this study. The THz results obtained were compared to results obtained from XRD and DSC measurements. Whereas DSC measurements failed to reliably detect crystalline API in the smartFilms, XRD and THz-spectroscopy showed similar results and revealed that it was possible to prepare smartFilms loaded with >23% (w/w) amorphous API. Results indicate the great potential of THz spectroscopy for the non-destructive determination of the crystalline state of APIs in smartFilms and/or tablets made from paper.