Pharmaceutical Technology: Controlled Drug Release, Volume 2

MULTIPARTICULATES [CH. 12 135
Fig. 3—Influence of thermal treatment on the drug release from tablets containing 15% HMW DL-PLA, 60%
theophylline and 25% microcrystalline cellulose.
The data in Figs 5 and 6 show dissolution profiles of theophylline from tablets containing low
molecular weight DL-PLA. These profiles demonstrated that there was no significant difference in
the dissolution release rate between the heated and non-heated tablets for both the 25% and the
60% theophylline formulations. In all cases, the tablets disintegrated within minutes and 100% of
the theophylline was released within 1h. These results suggested that, regardless of the thermal
treatment, low molecular DL-PLA had less of a binding capacity than the high molecular weight
DL-PLA. Although thermal treatment increased the hardness of the tablet, it still rapidly
disintegrated in water at 37°C. Dissolution studies were conducted at 37°C, which is above the
glass transition temperature of the low molecular weight DL-PLA. The T g of this polymer is 27°
C. Above the glass transition temperature, the chains of the polymer become more flexible and
may loosen the binding capacity of the polymer in the tablet matrix, as evidenced by the rapid
disintegration of the tablets when exposed to water at 37°C.
The dissolution profiles in Figs 7 and 8 for theophylline tablets containing a low molecular
weight L-PLA, microcrystalline cellulose, and theophylline. Thermal treatment had no significant
effect on the dissolution profiles from tables containing 25% theophylline (Fig. 7). As with the
tablets containing low molecular weight DL- PLA, these tablets disintegrated rapidly, releasing
100% theophylline within 1 h. However, the dissolution rate of theophylline from tablets
containing 60% drug was accelerated from the thermally treated tablets when compared with the
non-thermally treated tablets (Fig. 8). Although these tablets disintegrated within hours, the