Controlled-release of diclofenac sodium from wax matrix granule

A twin-screw compounding extruder was used to prepare wax matrix granules (WMG) consisting of carnauba wax, diclofenac sodium (DS) as a model drug, and rate-controlling agents such as hydroxypropylcellulose (HPC-SL), methacylic acid copolymer L (Eudragit L-100), and sodium chloride (NaCl). In this preparation, a wax matrix with high mechanical strength was obtained even at temperatures lower than the wax melting point. Dissolution behaviors of DS from WMG were strongly influenced by granule formulation, in which an increase in the content of HPC-SL or Eudragit L-100 brought a significant increase in the dissolution rate. The extent of this enhancing effect in HPC-SL was identical in two different dissolution mediums (pH 6.8 buffer solution and water), but in Eudragit L-100 was more significant in pH 6.8 buffer solution than in water. Only a small increase in the dissolution rate was observed in NaCl-containing WMG. These different behaviors were attributed to the physicochemical properties (i.e. swelling and solubility) of the rate-controlling agent in the dissolution medium. Further, mechanical strengths of the wetted WMG after dissolution studies were > 70 g/mm² suggesting that burst release of DS in the gastrointestinal tract would be avoided.