Drug Discov Ther. 2008;2(1):45-51.

A new method of preparing TRH derivative-loaded poly(dl-lactide-coglycolide) microspheres based on a solid solution system.

Matsumoto A, Matsukawa Y, Nishioka Y, Harada M, Horikiri Y, Yamahara H

We investigated a new method of preparing peptide-loaded poly(dl-lactide-co-glycolide) microspheres with high encapsulation efficiency, low initial burst, and long-term sustained release by dissolving a peptide in a polymer by applying a solid solution system to the preparation of an oil phase. Solid solutions were prepared by dissolving a polymer (poly(dl-lactide-co-glycolide)) and a peptide (TRH derivative) in mixed solvents and then evaporating the solvents. Microspheres were prepared by an O/W emulsion solvent evaporation method, using the solution of the solid solution in dichloromethane as an oil phase. The state of the peptide in the solid solution and in the microspheres was evaluated by X-ray diffraction analysis. Release of the peptide from the microspheres was evaluated by an in vitro drug release test. Observation of the oil phase, X-ray diffraction analysis, and DSC analysis revealed that the peptides were dispersed in a molecular state in the solid solution and in microspheres with peptide loading of up to 15%. Encapsulation efficiency was over 90% for microspheres with peptide loading of up to 15%. The release of the peptide from the microspheres lasted over 21 days at least with the limited initial burst in vitro. High encapsulation efficiency, low initial burst, and long-term sustained release can be accomplished with microspheres prepared by a method based on a solid solution system.

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