| In this dissertation, we investigated a new method for preparing drug-containing microspheres using succinylsulfathiazole as a model drug and ethylcellulose (in the form of aqueous colloidal dispersion) as the matrix polymer. The organic polymer solution in traditional emulsion-solvent evaporation method to prepare microspheres was replaced with aqueous ethylcellulose dispersion to minimize the use of organic solvent.; Chapter one provides background information concerning the model drug, aqueous coating material, film forming mechanism, plasticizers, sustained-release formulation and microencapsulation.; Chapter two describes methods for extracting and analyzing four commonly used plasticizers, namely dibutyl sebacate, triethyl citrate, triacetin and diethyl phthalate, in microspheres by using high performance liquid chromatography. The methods show excellent recoveries, precisions and sensitivities.; Chapter three describes the methods to prepare and evaluate drug-containing microspheres. Four different plasticizers were used separately to plasticize the aqueous ethylcellulose dispersion before formation of microspheres and in the curing process after the microspheres were formed. The morphology, the closed-space porosity, the surface area and the in-vitro dissolution profile are also described in this chapter. The effects of drug content, particle size, plasticizer content and different plasticizers on the dissolution profile are studied. When dibutyl sebacate is used as plasticizer and drug loading was lower than 10% (w/w), the microspheres have smooth surfaces and good sustained release. The time of 50% release increases from 10 minutes to 9 hours when the drug content are decreased from 21.7% to 5.4%. The dibutyl sebacate content has greater effect on the dissolution profiles of the microspheres than other plasticizers.; The process conditions have great effects on the characteristics and dissolution rate of the microspheres. Therefore, a two-level three-factor complete experimental design was used in studying the significance of the concentration of plasticizer (diethyl phthalate) in the outer phase, process temperature and the curing time. Increasing processing temperature from 55{dollar}spcirc{dollar}C to 65{dollar}spcirc{dollar}C has a very significant prolonged effect on the time for 50% drug release. Increasing the amount of diethyl phthalate in the outer phase and increasing the curing time also has significant effect on time for 50% drug release. These results are presented in chapter 4. |
