Pharmaceutical Technology: Controlled Drug Release, Volume 2

MULTIPARTICULATES [CH. 10 121
Fig. 2—Effect of polyisobutadiene concentration on in vitro release of theophylline microcap-sules (theophylline:
RSPM ratio, 1:2; particle size , 540 µm): □, 2.0% (w/w); ∆, 2.5% (w/w); ○, 3.0% (w/w); ●, 4.0% (w/w).
Lowering the viscosity of the coating medium resulted in an increased degree of aggregation of
the micromatrices. Increasing the viscosity produced a higher percentage of large unacceptable
micromatrices. The stirring speed was found to be the most important factor contributing to the
size distribution of the micromatrices. The percentage of small particles increased at higher stirrer
speed.
In vitro dissolution at increasing pH allows a comparison to be made between the different
microcapsules prepared with various core:wall ratios. The drug dissolution from the
microcapsules depends on the core:coat ratio and the rate of drug release decreases with a
decrease in core:coat ratio.
From preliminary results, the presence of polyisobutadiene at a minimum concentration was
essential for the production of free-flowing, discrete microcapsules. A concentration of
polyisobutadiene of more than 2.5% was found to be suitable to give good, reproducible,
microcapsules (Figs 1–3). The coacervated polymer droplet formed a smooth continuous coat
around each particle, markedly different from the surface characteristics of pure drug. The
mechanism of coacervated droplet stabilization could be that the polymer adsorption layers around
the particles are quite dense and hence the particles undergo pseudoelastic collision, an approach
rather than a mixing of their adsorption layers.
The drug release profile was plotted against time (Figs. 4 and 5) and it was observed that the
release kinetics followed both first-order and Higuchi equations up to 75–80% of the cumulative
drug release. The micromatrices followed the Higuchi equation (NONLIN package).