Eudragit RS microspheres containing pipemidic acid, as a model drug, were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The aim of the work was to evaluate the influence of stirring rate on the average particle size, particle morphology, drug content and release kinetics, as well as the influence of particle size on microsphere morphology, drug content and release kinetics. Stirring rate has been found to significantly influence the average diameter of microspheres. The average diameter decreases as the stirring rate increases. This can be explained by production of a finer dispersion of droplets when higher stirring rates are applied and, consequently, by the formation of smaller microspheres. With increasing stirring rate and increasing fraction particle size the drug content also increases. It is assumed that this dependence is a consequence of an uneven diffusion of the drug from the inner to the outer emulsion phase, and an uneven encapsulation of drug particles during the preparation. Drug release follows the Higuchi model. As seen from SEM photographs, larger microspheres are more porous and the microspheres produced at higher stirring rates are more porous than those produced at lower stirring rates. This explains the unexpected finding that the release rate increases as the fraction particle size and the stirring rate increase.
Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.
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