a method of forming microspheres containing a hydrophilic drug or agent for injection to provide localized treatment over a protracted time with sustained delivery in a therapeutically indicated rate band . the drug or agent is first dispersed or suspended as a micropulverized solid in an inert hydrophobic oil and sonicated with a non - aqueous solution of a biodegradable polymer . the dispersion is then stabilized in a second oil to remove solvent from the microspheres . non - aqueous solvents are used throughout , and high drug concentrations are obtained simultaneously with enhanced control over a uniform and sustained delivery rate with extended duration of delivery . in vitro studies of ganciclovir in a silicone oil / fluorosilicone oil / plga system yield microsphere fractions that provide dose levels in a therapeutic range for cmv retinitis from only a single intravitreal injection that lasts substantially in excess of one month . the preparation method allows drug loading efficiencies above ninety percent . by protecting the drug in an inner phase carrier of biocompatible but not biodegradable oil , and forming biodegradable shells and pore - defining foliations within the microspheres , the rate of control of solvent erosion pathways into the microspheres is extended , and selection of the polymer and of the oils allow control over both the delivery rate and time .