Preparation and uses of multi-phase microspheres

A method for preparing multi-phase microspheres containing a protein, peptide, or dug comprising:

• mixing an aqueous solution of the protein, peptide, or drug with a fixed oil to form a W/O microemulsion;
• mixing polylactic acid or polylactic glycolic acid and a polymer solvent together to form a polymer solution;
• dispersing the microemulsion into the polymer solution to form a W/O/"O" emulsion;
• mixing the W/O/"O" emulsion together in a dispersion oil which is incompatible with the polymer solvent to form a multiple emulsion;
• agitating and removing the solvent from the multiple emulsion to form hardened microspheres;
• and
• washing and drying the hardened microspheres to form multi-phase microspheres containing the water-soluble protein, peptide, or drug.

A method for preparing microspheres containing a water-soluble drug comprising:

• preparing a first mixture of a water-soluble drug in water, gelatin and Tween 80 to form an aqueous phase;
• preparing a second mixture of an amount of aluminum stearate and a volume of a fixed oil to produce a 2% w/w aluminum stearate and about 5% w/w Span 80 oil phase;
• combining the first mixture with the second mixture to form a coarse W/O emulsion;
• processing the coarse W/O emulsion into a fine W/O microemulsion;
• preparing a third mixture of polylactic acid or polylactic glycolic acid and a solvent;
• combining a quantity of the fine W/O microemulsion with the third mixture to form a W/O/"O" emulsion;
• preparing a fourth mixture of an amount of Span 80 and an oil incompatible with the polymer solvent;
• pouring the W/O/"O" emulsion into the fourth mixture to form a multiple emulsion;
• agitating and evaporating the polymer solvent from the multiple emulsion to form hardened microspheres;
• separating the hardened microspheres from the mixture;
• and
• washing and drying the hardened microspheres to form multi-phase microspheres containing a water-soluble drug.

A multi-phase microsphere for the delivery of a peptide, protein, or drug comprising a biodegradable essentially water insoluble polymeric matrix of polylactic acid or polylactic glycolic acid surrounding a protein, peptide, or drug contained within a fixed oil, said microsphere prepared by a process of:

• preparing a first mixture of a water-soluble protein, peptide, or dug in water, gelatin and Tween 80 to form an aqueous base;
• preparing a second mixture of an amount of aluminum stearate and a volume of a fixed oil to produce a 2% w/w aluminum stearate and about 5% w/w span 80 oil phase;
• combining the first mixture with the second mixture to form a coarse W/O emulsion;
• processing the coarse W/O emulsion into a fine W/O micro emulsion;
• preparing a third mixture of a biodegradable essentially water-insoluble polymer polylactic acid of polylactic glycolic acid and a solvent;
• combining a quantity of the fine W/O micro emulsion with the third mixture to form a W/O/"O" emulsion;
• preparing a fourth mixture of an amount of span 80 and an oil incompatible with the polymer solvent;
• pouring the W/O/"O" emulsion into the fourth mixture to form a multiple emulsion;
• evaporating the solvent from the multiple emulsion to form hardened microspheres;
• separating the hardened microspheres from the mixture;
• and
• washing and drying the hardened microspheres to form multi-phase microspheres containing a water-soluble protein, peptide, or drug.