FLUIDIZED-BED SPRAY COATED POROUS HYDROGEL BEADS FOR SUSTAINED-RELEASE OF DICLOFENAC SODIUM

Swellable porous hydrogel beads were loaded with diclofenac sodium and then coated with pseudo-latex ethylcellulose (EC) in a fluidized-bed spray coater. The drug release profile in-vitro can be modified by add ing 25% or more triethyl citrate (TEC) or dibutyl sebacate (DBS) as a plasticizer. The plasticized coating film can overcome the swelling st ress of the core and function as a barrier for sustained drug release. Adding TEC resulted in a near-zero order kinetics after an initial bu rst in the release profile, and adding DBS showed a first initial burs t, a second stage of linear release, a third stage of slow release. Th e initial burst is due to the flaws or cracks on the surface of the co ated-beads and it can be reduced by increasing the amount of plasticiz er or film thickness and also by adjusting the thermal treatment time. A 4- to 6-h treatment at 60 degrees C was found to be the optimal con dition to give the smallest initial burst for coating film containing TEC as a plasticizer. Adding hydrophilic hydroxylpropyl methylcellulos e (HPMC) could smooth the initial burst and change the release profile to a Fickian-type release, and in this case increasing the thermal tr eatment time could reduce the release rate. Two kinds of EC-coated bea ds were tested in-vivo by using rabbits as animal models and showed go od sustained release behaviors as the drug concentration in plasma cou ld be maintained above 0.4 mu g/ml and lower than 1.5 mu g/ml for 24 h . (C) 1997 Elsevier Science Ireland Ltd.