title: Dissolution mechanism of diclofenac sodium from wax matrix granules.
abstract: Dissolution behavior of diclofenac sodium (DS) from wax matrix granules (WMGs) prepared using a twin-screw compounding extruder is closely related to swelling ability and solubility of the rate-controlling agent employed. A swellable and soluble (hydroxypropyl)-cellulose (HPC-SL) generates both an expansion of pores inside WMGs and a structural change observed as cracking on the surface of WMGs. These changes are confirmed by mercury porosimetry. Release of DS was increased with an increase in the amount of HPC-SL in WMGs, but only 35% of DS was released from WMGs containing 73% (w/w) NaCl at the 24 h point of the dissolution. Further, no cracking was observed on the surface of NaCl-containing WMGs. A linear relationship between mean dissolution time (MDT) of DS for WMGs containing different types of HPC (HPC-SL, -M, and -H) and swelling abilities suggests that release of DS could be directly controlled by swelling of HPCs. In addition to this result, an application of the exponential model (Mt/M infinity = kt(n)) introduced by Ritger and Peppas (J. Controlled Release 1987, 5, 23-36) to DS release indicates that case II release plays a critical role in HPC-SL-containing WMGs and Fickian release is predominant in NaCl-containing WMGs since the values of n of WMGs containing 73% (w/w) NaCl and 40% (w/w) HPC-SL are 0.41 and 0.71, respectively. These results suggest that proper selection of rate-controlling agents based on their physicochemical properties (such as swelling ability and solubility) is important in designing WMGs with desired dissolution profiles.
authors.affiliation: Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Miyagawa
authors.forename: T
authors.initials: T
authors.lastname: Okabe
authors.forename: M
authors.initials: M
authors.lastname: Miyajima
authors.forename: H
authors.initials: H
authors.lastname: Sunada
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004008:Diclofenac / Q000737:chemistry*; D007700:Kinetics; D012995:Solubility
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D002482:Cellulose; C008079:hydroxypropylcellulose