A controlled release system and manufacturing method is provided. The method comprises providing a first aqueous solution containing a hydrophilic drug and an alkaline agent, providing an organic solution containing a hydrophobic molecule, providing a second aqueous solution containing a hydrophilic surfactant, mixing the first hydrophilic solution with the organic solution to form a first emulsion, and mixing the first emulsion with a second aqueous solution to form a second emulsion containing delayed-release microsphere.