Viscosity of the continuous phase and other factors in the optimization of matrix microsphere formulations prepared by emulsion-solvent evaporation
Williams, Mervin Lee
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The objective of this study was to examine the effect of the continuous phase viscosity and other formulation factors on microsphere properties. Matrix microspheres were prepared using emulsion-solvent evaporation; anhydrous theophylline was incorporated as the model drug. The theoretical drug loading range was 33.3 % for most of the formulations. Eudragit® polymers (Eudragit® RL 100, Eudragit® RS 100), and ethylcellulose polymers (ETHOCEL® 100, ETHOCEL® 20) were used to prepare different concentrations of polymer in acetone. It was discovered that at Eudragit® polymer concentrations of 27 % in acetone, with light mineral oil as the external phase, produced larger particle sizes and wider range of particle sizes. Furthermore, the microspheres that were formulated did not have immediate release, especially at the larger particle sizes (the release was slower). This was in contrast to Eudragit® polymer concentrations of 27 % in acetone, that used heavy mineral oil as the external phase, where smaller particle sizes and immediate release was common. However, it was demonstrated that larger particle sizes could be attained in heavy mineral oil by increasing the polymer concentration and the polymer phase viscosity through the incorporation of two polymers (Eudragit® RL 100/ ETHOCEL® 100) in acetone and mixing them at a substantially higher rpm. Furthermore, there was a considerable difference in microsphere size and the range of particle sizes between ETHOCEL® polymer concentrations using heavy mineral oil, and ETHOCEL® polymer concentrations using light mineral oil. Light mineral oil preparations had a tendency to favor larger particle sizes and a wider range of microsphere sizes. Calculated geometric mean diameters in light and heavy mineral oil indicated that average microsphere size was at least three times higher in light mineral oil preparations. In addition, the drug release rates from microspheres prepared with a higher molecular weight polymer of ETHOCEL® 100 were uncharacteristically faster than release from microspheres prepared from lower molecular weight ETHOCEL® 20. This was attributed to the presence of aggregates of small particles, hollow shell-like particles, and smaller particles that were attached to the larger particle sizes.