A method to control particle size of cellulose acetate trimellitate microspheres.

Abstract

A method for controlling microsphere particle size by regulating the ratio of polymer to solvent concentration and volume fraction, for an emulsion-solvent removal type of microencapsulation system, has been investigated. Viscosity of the external phase was kept constant by using light mineral oil in all experiments. Viscosity of the polymer solution, the internal phase, was modified by changing the ratio of the polymer to solvent concentration. Microspheres were obtained by adding the internal phase to the external phase and stirring the mixture for 30 min. A non-solvent was then added to the system to harden the polymer and recover the microspheres. Polymer concentration was modified by adding extra solvent to the mineral oil, just before the addition of the internal phase and also by adding extra solvent to the polymer phase. Similar, but not identical, results were obtained in both of these systems. A plot of particle size versus polymer to the solvent ratio resulted in sigmoidal curves. The term solvent means the solvent available to the polymer after mixing with mineral oil. A separate curve was obtained for each polymer concentration used in the experiments. When the internal phase volume fraction was incorporated as a variable in the plot of particle size, the three sigmoidal curves merged into a single curve, irrespective of the polymer concentration. The equation developed for controlling the particle size, as a function of polymer and solvent concentration and phase volume ratio, also was tested in systems that contained tartrazine as a model drug. Dissolution experiments were carried out and dissolution rate was correlated to particle size. Microspheres size was controlled by polymer and solvent concentration and phase volume ratio.