Pharmaceutical Technology: Controlled Drug Release, Volume 2

122 CH. 10] CONTROLLED DELIVERY OF THEOPHYLLINE
Fig. 3—Effect of polyisobutadiene concentration on in vitro release of theophylline microcapsules (particle size , 540
µm). Theophylline: S 100 ratio of 1:2: ▲, 4.0% (w/w); ●, 3.0% (w/w); ■, 2.5% (w/w). Theophylline: L 100 ratio of 1:
2; ∆, 4.0% (w/w); ○, 3.0% (w/w); □, 2.5% (w/w).
The plasma concentration of theophylline following oral administration of Eudragit RS 100
microcapsules reached a peak at 7.1 h and decreased by a monoexponential process. This dosage
form exhibited maximum prolongation. The plasma bioavailability parameters are listed in
Table 3. There were significant differences in the AUC, C max and T max among the dosage forms. The
drug release profiles of the polymers, as revealed from in vitro dissolution, showed correlation
with the in vivo bioavailability parameter. Micromatrices were found to be the better dosage form
for the prolongation of drug release.
Because of the pH-independent dissolution profile of Eudragit RS 100 and RSPM, the dosage
forms prepared with these polymers offer better controlled release kinetics than those with S 100
and L 100, as the solubilities of the latter are pH dependent.
In conclusion, the developed controlled release dosage forms of theophylline are capable of
maintaining effective therapeutic blood levels of the drug. Administration 12 hourly of these
dosage forms to a healthy volunteer, gave a relatively high bioavailability, a relatively low
difference between the maximum and minimum serum concentrations and a relatively small serum
concentration is expected to occur provided that the dosage forms are taken in the non-fasting
state.
REFERENCES
1 [] L.Hendeles and M.Weinberger, Pharmacotherapy, 3, 2 (1983).
2 [] C.H.Feldman, V.E.Hutchinson, T.H.Sher, B.R.Feldman and W.J.Davis, Ther. Drug Monit., 4, 69 (1982).