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The possibility to compress ordinary paper into tablets was systematically investigated in this study. Results proved that tablets can be made from paper, independent of the type of paper used. The tablets appear shiny and with a smooth surface. The pharmaceutical quality was acceptable, i.e. all tablets fulfilled the requirements for tablets according to the European Pharmacopeia. Drug-loaded tablets were produced by compression of drug-loaded paper. Drug loading did not alter the pharmaceutical quality. However, the uncoated tablets possessed an extremely fast disintegration, i.e. intense swelling upon contact with water, which might hamper the swallowing after oral administration. To avoid swelling tablets were successfully coated with a polymer film, leading to a prevention of swelling but immediate disintegration in simulated gastric fluid. In fact, tablets made from paper are a novel and promising strategy for improved oral drug delivery. They can be easily produced without any further excipients and possess pharmaceutical quality according to the European Pharmacopeia.

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.

Experiments were conducted to illustrate some of the challenges associated with measuring dynamic MDI aerosols. Experimental HFA-134a solution MDIs containing 8 or 20% ethanol were measured using the Andersen cascade impactor using three different inlets. It was demonstrated that the size distribution of MDI aerosols changes substantially during the measurement process. The measured size distribution was shown to be dependent on the degree of evaporation that has occurred prior to size measurement. Additionally, the degree of evaporation prior to measurement also influences the number of modes present in the measured size distribution. While MDI aerosols appeared to have a separate large particle mode when measured using the U.S. Pharmacopeial induction port ("USP inlet"; [U.S. Pharmacopeia, 1996. Physical tests and determinations601aerosols, metered dose inhalers, and dry powders. Pharmacopeial Forum 22, pp. 3065-3095]), the aerosols were shown to be monomodal when measured using a large volume inlet. The apparent large particle mode observed with the USP inlet seem rather to be droplets from the same monomodal distribution that have not fully evaporated. The complex interaction of the MDI plume and inlet configuration was described. Inlet design was shown to influence inlet deposition, measured particle size, and even deposition in the actuator mouthpiece. Inlet deposition was shown to be highly size-dependent with large droplets being collected more efficiently than smaller droplets.

This study was conducted to evaluate the pretreatment effects of different in vivo moxibustion on the permeation of a model high molecular compound, FITC-dextran, with a mean molecular weight of 4 kDa (FD-4), through excised hairless rat skin. Direct or indirect moxibustion (0.10 g moxa) was pretreated consecutively 4 times every 5 min on the abdomen of hairless rats, and the permeation of FD-4 was determined through the excised skin over 8h from 30 min after starting the first moxibustion. This consecutive moxibustion pretreatment showed a significant increase in the skin temperature as well as skin permeation of FD-4 compared with the control group (no moxibustion pretreatment). Quantitative parameters showed an increase in skin temperature and skin permeation: the area under the skin temperature over control temperature-time curve during one burning cycle (5.0 min) (AUCtemp) or the maximum skin temperature during moxibustion (Tmax) and the cumulative amount of FD-4 permeated through skin over 8h (Q8) or steady-state flux were increased by moxibustion pretreatment. Then, the effect of pedestal thickness (distance from the moxa cylinder and skin surface), shape of the moxa cylinder (5mm diameter, 13 mm height or 9 mm diameter, 7 mm height), burning materials (moxa or aromatic incense), pedestal component (paper, potato or ginger) and moxibustion pretreatment method (direct or indirect moxibustion) was evaluated on the AUCtemp or Tmax and Q8 or flux. The amount of protein leached from the skin surface was also determined as an inflammatory index by this moxibustion pretreatment. When the skin temperature was increased to 60 degrees C, the Q8 or flux as well as the amount of protein leached were markedly increased. When the skin temperature was controlled to 42 to 45 degrees C by an adequate selection of pedestal thickness, shape of the moxa cylinder, burning materials, pedestal component and moxibustion pretreatment method, on the other hand, protein leaching remained unaltered, but the Q8 or flux significantly increased with the Tmax. This study thus provides credible evidence that moxibustion pretreatment increases the skin permeation of high molecular compounds.