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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 cs 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.

We combined conventional inkjet printing technology with flexographic printing to fabricate drug delivery systems with accurate doses and tailored drug release. Riboflavin sodium phosphate (RSP) and propranolol hydrochloride (PH) were used as water-soluble model drugs. Three different paper substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer. The printed APIs were coated with water insoluble polymeric films of different thickness using flexographic printing. All substrates were characterized with respect to wettability, surface roughness, air permeability, and cell toxicity. In addition, content uniformity and release profiles of the produced solid dosage forms before and after coating were studied. The substrates were nontoxic for the human cell line assayed. Substrate B was smoothest and least porous. The properties of substrates B and C were similar, whereas those of substrate A differed significantly from those of B, C. The release kinetics of both printed APIs was slowest from substrate B before and after coating with the water insoluble polymer film, following by substrate C, whereas substrate A showed the fastest release. The release rate decreased with increasing polymer coating film thickness. The printed solid dosage forms showed excellent content uniformity. So, combining the two printing technologies allowed fabricating controlled-release oral dosage forms that are challenging to produce using a single technique. The approach opens up new perspectives in the manufacture of flexible doses and tailored drug-delivery systems.

Poly(ethyleneimine) (PEI) microcapsules containing laccase from Trametes hirsuta (ThL) and Trametes versicolor (TvL) were printed onto paper substrate by three different methods: screen printing, rod coating, and flexo printing. Microcapsules were fabricated via interfacial polycondensation of PEI with the cross-linker sebacoyl chloride, incorporated into an ink, and printed or coated on the paper substrate. The same ink components were used for three printing methods, and it was found that laccase microcapsules were compatible with the ink. Enzymatic activity of microencapsulated TvL was maintained constant in polymer-based ink for at least eight weeks. Thick layers with high enzymatic activity were obtained when laccase-containing microcapsules were screen printed on paper substrate. Flexo printed bioactive paper showed very low activity, since by using this printing method the paper surface was not fully covered by enzyme microcapsules. Finally, screen printing provided a bioactive paper with high water-resistance and the highest enzyme lifetime.