Ym. Sun et al., FLUIDIZED-BED SPRAY COATED POROUS HYDROGEL BEADS FOR SUSTAINED-RELEASE OF DICLOFENAC SODIUM, Journal of controlled release, 47(3), 1997, pp. 247-260
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.