Methods for fabrication, uses and compositions of small spherical particles prepared by controlled phase separation

A method for preparing small spherical particles of an active agent, the method comprising the steps of:

• dissolving the active agent and a phase-separation enhancing agent in an aqueous or aqueous-miscible solvent to form a solution of a single continuous phase, and
• cooling the solution to thereby form a suspension comprising solid, small spherical particles of the active agent in a liquid phase comprising the phase-separation enhancing agent, wherein said cooling is performed at a controlled rate from about 8.6° C./minute to about 26.5° C./minute, wherein said active agent is a macromolecule, and wherein the particles have an average particle size of from about 0.5 μm to about 10 μm.

A method for preparing solid, small spherical particles of active agent comprising:

• providing an aqueous solution in a single liquid phase and comprising the active agent and a phase separation enhancing agent;
• cooling the aqueous solution;
• thereby forming a suspension comprising solid, small spherical particles of active agent suspended in a liquid phase comprising the phase separation enhancing agent and water, the solid, small spherical particles being substantially spherical, wherein said cooling is performed at a controlled rate from about 8.6° C./minute to about 26.5° C./minute, wherein said active agent is a macromolecule, and wherein the particles have an average particle size of from about 0.5 μm to about 10 μm.