Stabilization of sodium guaiazulene sulfonate in granules for tableting prepared using a twin-screw extruder

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 56; no. 3; pp. 347 - 354
• Main Authors: Nakamichi, Kouichi, Nakano, Tomio, Yasuura, Hiroyuki, Izumi, Shogo, Kawashima, Yoshiaki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2003; Elsevier Science
• Subjects: A twin-screw extruder; Azulenes; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Drug Stability; General pharmacology; Hot Temperature - adverse effects; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Sesquiterpenes - chemical synthesis; Sodium guaiazulene sulfonate; Stabilization; Tablets; Technology, Pharmaceutical - instrumentation; Technology, Pharmaceutical - methods; The kneading paddle elements; Uniformly dispersing; Water; Water; A twin-screw extruder; Uniformly dispersing; Stabilization; Sodium guaiazulene sulfonate; The kneading paddle elements; Extruder; Stability; Pharmaceutical technology; Methodology; Antiinflammatory agent; Sodium; Formulation; Preparation; Tablet; Granule; Physicochemical properties
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/S0939-6411(03)00100-0

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 °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.