Am. Dyer et al., EFFECT OF POLYMER LOADING ON DRUG-RELEASE FROM FILM-COATED IBUPROFEN PELLETS PREPARED BY EXTRUSION-SPHERONIZATION, Drug development and industrial pharmacy, 21(16), 1995, pp. 1841-1858
Many factors are capable of influencing the mechanism of drug release
from pellets prepared by extrusion-spheronization. This study was desi
gned to elucidate the effect of polymer type and loading and the effec
t of processing variables on the rate and mechanism of drug release fr
om ibuprofen pellets coated using aqueous polymeric dispersions. Quali
tative and quantitative assessment of the success of the film coating
process and the quality of the resultant films is made using scanning
electron microscopy and in-vitro dissolution testing The importance of
plasticizer in polymeric film formation is also discussed. Uncoated p
ellets containing 60, 70 and 80% ibuprofen were coated with aqueous po
lymeric dispersions of polymethacrylates, ethylcellulose and silicone
elastomer films The high drug loading of these pellets adds special in
terest to this study. Drug release from uncoated pellets appears to fo
llow first-order kinetics. The application of a polymeric membrane to
uncoated cores has the effect of retarding drug release. There appears
to be a critical coating level below which core coverage by the polym
er is incomplete, drug release is diffusion controlled and first-order
release kinetics are observed. Above a defined polymer level, drug re
lease appears to be membrane controlled and zero-order kinetics are ob
served. The presence of plasticizer in the polymeric film imparts a hy
drophilic component to an otherwise hydrophobic membrane. This enhance
s the penetration of aqueous solvent into the pellet core during in-vi
tro dissolution testing increasing the rate of drug release. Scanning
electron micrographs reveal the nature of these hydrophilic pores, ben
eath which a fine tortuous skeletal network of drug-depleted core is e
xposed.