Si. Pather et al., SUSTAINED-RELEASE THEOPHYLLINE TABLETS BY DIRECT COMPRESSION PART-1 -FORMULATION AND IN-VITRO TESTING, International journal of pharmaceutics, 164(1-2), 1998, pp. 1-10
In an effort to reduce production costs, a simple, direct compression
sustained release formulation consisting, principally, of the drug (th
eophylline) and ethylcellulose was investigated. Ethylcellulose compac
ts well and also retards drug release. In addition, matrices of this p
olymer display slow surface erosion which can be enhanced by the incor
poration of a swelling agent. This property was utilized in an attempt
to decrease the attenuation of the release rate that is observed with
matrix tablets that follow the Higuchi pattern of drug release. The r
elease rate decreases because the external layers of the tablet become
depleted and water must penetrate the deeper layers of the tablet to
reach the remaining drug, The theophylline to ethylcellulose ratio and
the tablet hardness were found to influence the rate of drug release.
It was possible to sustain the release of a therapeutic dose of theop
hylline over a 12-h period. Mathematical modeling showed an equally go
od fit between the data and (a) the Higuchi model, or (b) a model that
took into account diffusion, relaxation of the polymer, and erosion.
However, the shape of the release curve was altered slightly in those
tablets that eroded to a greater extent and residuals analysis illustr
ated a better fit with the latter model. The erosion mechanism can be
used to lessen one of the major problems associated with hydrophobic a
nd plastic matrix tablets, i.e. the continuous reduction in the termin
al release rate with time. (C) 1998 Elsevier Science B.V. All rights r
eserved.