Increases in plasma kallikrein-like and pancreas kallikrein-like substances after administration of pancreas or plasma kallikrein.

Differences between the concentration of a kallikrein-like substance in blood obtained by the peptide-MCA method and that obtained by the TAME (N-tosyl-l-arginine methyl ester) method by administering pancreas kallikrein to rabbits have been recognized already and the existence of a Substance X was evaluated. In the present study, it was revealed that administration of pancreas kallikrein resulted in inactivation of kallikrein in the substrate in gut homogenates and homogenates of various organs except for the pancreas. In the pancreas homogenate, inactivation was not observed. On the other hand, there was a possibility that at least part of Substance X existed due to plasma kallikrein. Thus, the concentration of plasma kallikrein in plasma after administration of pancreas kallikrein was determined. A pattern similar to the concentration curve of Substance X was obtained. Thus, it was clarified that plasma kallikrein-like substance, at least, increased when pancreas kallikrein was administered. On the contrary, when plasma kallikrein was administered to the rabbit duodenum, the concentration of pancreas kallikrein-like substance in plasma increased. It was also clarified that plasma kallikrein-like substance increased in vitro by adding pancreas kallikrein to the blood or plasma, whereas the in vitro addition of plasma kallikrein to the blood induced its decomposition and a slight increase in pancreas kallikrein-like substance, and the addition of plasma kallikrein to the plasma induced an increase in plasma kallikrein and a slight increase in pancreas kallikrein-like substance.

Prediction of tableting problems such as capping and sticking: theoretical calculations.

Tabletability factors were developed through the use of an automated tabletability tester, and the applicability of these factors to actual manufacturing procedures was tested by the large-scale manufacturing of tablets. Use of this approach does not require knowledge of the tablet's physical properties, e.g., moisture content, porosity, particle size, fluidity, and angle of repose.