Kazuyuki Ishikawa

Improvement of the agitation granulation method to prepare granules containing a high content of a very hygroscopic drug.

This study describes a new approach to the preparation of a granulate with a high content of a very hygroscopic powder or drug, using the agitation granulation method, and the development of a tablet formulation using these granulates. A Chinese medicine extract, Hatimi‐zio‐gan, was used as the model of a very hygroscopic drug. Among the several excipients tested, only porous calcium silicate could be used to prepare granules, with a mixing ratio (extract to porous calcium silicate) from 2:1 to 20:1. With other excipients, very large lumps were formed during the granulation process. The best mixing ratio of extract to porous calcium silicate was 6:1. For preparation of the granules, water could be added to the mixed powder within a range of 1‐ to 4‐times the amount of porous calcium silicate. From these results, it was concluded that the ability of porous calcium silicate to hold large amounts of water in its numerous pores may allow for the preparation of granulates with a high content of very hygroscopic drugs. Starch with partial α‐links, carboxymethyl starch sodium salt and crospovidone were used for selection of the disintegration agent. When crospovidone was used as a disintegration agent, tablets containing about 70% of the Chinese medicine extract disintegrated in less than 7 min, with good dissolution rates. The same process was applied to extracts of Hotyu‐ekki‐to, Syo‐seiryu‐to, Boi‐ogi‐to and Bohu‐tusyo‐san. The absorption of paeoniflorin, a characteristic monoterpene glucoside contained in Hatimi‐zio‐gan extract, was evaluated in beagle dogs after oral administration of the Hatimi‐zio‐gan tablets prepared in this study. The values of Cmax and AUC obtained after administration of the tablets prepared in this study were significantly greater than those obtained for commercial tablets.