Comparative studies on the influences of primary emulsion preparation on properties of uniform-sized exenatide-loaded PLGA microspheres.

PURPOSE: It is well known that primary emulsion (W1/O) preparation process (by ultrasonication or homogenization) plays an important role in the properties of drug-loaded microspheres, such as encapsulation efficiency, release behavior and pharmacodynamics. However, its involved mechanism has not been intensively and systematically studied, partly because that broad size distribution of the resultant particles prepared by conventional preparation can greatly disturb the analysis and reliability of the results. Here, we focused on the relevant studies. METHODS: In order to eliminate the disturbance caused by broad size distribution, uniform-sized exenatide-loaded poly(DL-lactic-co-glycolic acid) (PLGA) microspheres were prepared by Shirasu Porous Glass (SPG) premix membrane emulsification. The properties of microspheres whose W1/O was formed by ultrasonication (UMS) and homogenization (HMS) were compared including in vitro release, pharmacology and so forth. RESULTS: HMS exhibited fast release rate and hyperglycemic efficacy within first 14 days, but declined afterwards. Comparatively, UMS showed slower polymer degradation, more acidic microclimate pH (μpH) in vitro, and stable drug release with sustained efficacy during 1 month in vivo. CONCLUSIONS: HMS was desirable for the 2-week-sustained release in vivo, while UMS was more appropriate for the longer time release (about 1 month). These comparative researches can provide guidance for emulsion-microsphere preparation routs in pharmaceutics.