A detailed view of microparticle formation by in-process monitoring of the glass transition temperature

作者：Vay Kerstin^*; Friess Wolfgang; Scheler Stefan

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2012, 81(2): 399-408.

DOI：10.1016/j.ejpb.2012.02.019

• Glass transition temperature
• Microspheres
• Solvent evaporation
• PLGA
• Drug release

Biodegradable poly(D,L-lactide-co-glycolide) microspheres were prepared by a well-controlled emulsion solvent extraction/evaporation process. The objective of this study was to investigate how drug release can be modified by changing the morphology of the polymer matrix. The matrix structure was controlled by the preparation temperature which was varied between 10 and 35 degrees C, thus changing the 4 weeks release pattern from almost linear kinetics to a sigmoidal profile with a distinct lag phase and furthermore decreasing the encapsulation efficiency. By monitoring the glass transition temperature during the extraction process, it was shown that the preparation temperature determines the particle morphology by influencing the time span in which the polymer chains were mobile and flexible during the extraction process.
Further factors determining drug release were found to be the molecular weight of the polymer and the rate of solvent removal. The latter, however, has also influence on the encapsulation efficiency with slow removal causing a higher drug loss. A secondary modification of the outer particle structure could be achieved by ethanolic post-treatment of the particles, which caused an extension of the lag phase and subsequently an accelerated drug release.

• 出版日期2012-6