In vivo performance of a multiparticulate matrix, controlled-release theophylline preparation

An experimental multiparticulate matrix sustained-release theophylline preparation was evaluated in vivo, in comparison with Neulin-SR(R). Twelve healthy volunteers participated in the study, conducted according to a randomized, two-way crossover study design. The preparations were compared using the pharmacokinetic parameters, peak serum concentration (C-max, total area under the serum concentration-rime curve (AUC(0-infinity)), time to reach peak serum concentration (T-max), and time for 50% dose absorption in vivo (T-50%). A statistically significant difference was observed in the T-max and T-50% values (p < 0.05) but not in the logarithmic transformed values of C-max and AUC(0-infinity). These findings indicate that the two preparation are comparable in the extent but differ in the rate of absorption, with the experimental preparation being more sustained. In addition, the elimination rate constant (K-e), elimination half-life (t(1/2)), and apparent volume of distribution (V-d) of the drug were calculated. There was no statistically significant difference between the K-e, t(1/2), and V-d values obtained from the data of the two preparations. Moreover, the values obtained are comparable to those reported in the literature. A satisfactory correlation was also obtained between the mean in vivo absorption and mean in vitro dissolution data (p < 0.001) for both preparations.