CONTROLLED-RELEASE OF DICLOFENAC SODIUM FROM WAX MATRIX GRANULE

A twin-screw compounding extruder was used to prepare wax matrix granu les (WMG) consisting of carnauba wax, diclofenac sodium (DS) as a mode l drug, and rate-controlling agents such as hydroxypropylcellulose (HP C-SL), methacylic acid copolymer L (Eudragit L-100), and sodium chlori de (NaCl). In this preparation, a wax matrix with high mechanical stre ngth was obtained even at temperatures lower than the wax melting poin t. Dissolution behaviors of DS from WMG were strongly influenced by gr anule formulation, in which an increase in the content of HPC-SL or Eu dragit L-100 brought a significant increase in the dissolution rate. T he extent of this enhancing effect in HPC-SL was identical in two diff erent dissolution mediums (pH 6.8 buffer solution and water), but in E udragit L-100 was more significant in pH 6.8 buffer solution than in w ater. Only a small increase in the dissolution rate was observed in Na Cl-containing WMG. These different behaviors were attributed to the ph ysicochemical properties (i.e. swelling and solubility) of the rate-co ntrolling agent in the dissolution medium. Further, mechanical strengt hs of the wetted WMG after dissolution studies were >70 g/mm(2), sugge sting that burst release of DS in the gastrointestinal tract would be avoided.