Stabilization of sodium guaiazulene sulfonate in granules for tableting prepared using a twin-screw extruder.
Sodium guaiazulene sulfonate (GAS-Na), which has an anti-inflammatory effect, is an unstable compound, which is gradually decomposed in the solid state at room temperature. In fact, when heated (40 degrees C 6% RH), GAS-Na decomposes almost completely within 1 week. It was found that a kneaded mixture of GAS-Na and cornstarch (weight ratio; 1:250) for tableting with water is stable. So, during production, GAS-Na could be stabilized using water. Four kinds of tablet were prepared in different ways: direct tableting, tableting via screw granulation, tableting via fluidized bed granulation, and tableting via twin-screw extrusion. The stability of GAS-Na in these tablets was compared. The tablet prepared using screw granulation, during which 30% water was added to the material, was the most stable. It was, however, shown that reducing the water content to 12.5%, when screw granulation was conducted, made the GAS-Na less stable. Also, when a twin-screw extruder with kneading paddle elements in the screws was used even with lower water content of 12.5%, the stability of GAS-Na improved. In addition, when the kneading paddle elements were detached from the screws and only the feed screw elements were operated, GAS-Na lost its stability. These results show that the kneading paddle elements play a role in uniformly dispersing a small amount of water into the powder and stabilizing GAS-Na. It was found that the water presence was a very important factor with respect to the decomposition of GAS-Na, irrespective of the crystallinity. Furthermore, a twin-screw extruder with kneading paddle elements is useful for uniformly dispersing water to prepare stable formulations of GAS-Na.
Pharmaceutics Research Laboratory, Nippon Shinyaku Co., Ltd., Kyoto, Japan. k.nakamichi@po.nippon-shinyaku.co.jp
Kouichi
K
Nakamichi
Tomio
T
Nakano
Hiroyuki
H
Yasuura
Shogo
S
Izumi
Yoshiaki
Y
Kawashima
D052176:Azulenes; D004355:Drug Stability; D006358:Hot Temperature / Q000009:adverse effects; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
D052176:Azulenes; D012717:Sesquiterpenes; D013607:Tablets; C035058:azulene SN