DEVELOPMENT OF DICLOFENAC SODIUM CONTROLLED-RELEASE SOLID DISPERSIONSBY SPRAY-DRYING USING OPTIMIZATION STRATEGY .1. POWDER FORMULATION

Diclofenac sodium (DS) controlled release solid dispersions were prepa red by spray drying using ethylcellulose (EC), methacrylic acid copoly mer (Eudragit), chitosan, hydroxypropyl methylcellulose (HPMC), and ca rbomer as single carriers and EC-chitosan as combined carriers. Among solid dispersions of 3:1 drug:single carrier, the system containing ch itosan exhibited the slowest dissolution followed by the systems conta ining Eudragit, EC, HPMC, and carbomer, respectively. Combined carrier s of EC-chitosan exhibited more dissolution retarding effect than sing le carrier of EC or chitosan. An Hadamard matrix H[8] was employed to estimate the main effects of four parameters: spray feeding volume and contents of absolute ethanol, EC, and chitosan. Optimization strategy using multiple linear regression and a feasibility computer program w as utilized to obtain the optimum quantities of the four parameters th at would result in a required DS controlled release solid dispersion. The validation of the optimum DS solid dispersion was confirmed by sta tistical analysis. The optimized 10:(2.5+0.02) DS:(EC+chitosan) contro lled release solid dispersion exhibited a dissolution profile that was well fitted to Higuchi model.