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Comparative Studies on the Influences of Primary Emulsion Preparation on Properties of Uniform-Sized Exenatide-Loaded PLGA Microspheres

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Abstract

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.

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Acknowledgments and Disclosures

Feng Qi and Jie Wu contributed equally to this work. We thank the Joint NSFC/RGC grant (21161160555) for the financial support provided.

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Authors and Affiliations

  1. National Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China

    Feng Qi, Jie Wu, Dongxia Hao, Tingyuan Yang, Yu Ren, Guanghui Ma & Zhiguo Su

  2. University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Feng Qi

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  1. Feng Qi
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  2. Jie Wu
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  3. Dongxia Hao
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  4. Tingyuan Yang
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  6. Guanghui Ma
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  7. Zhiguo Su
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Correspondence to Guanghui Ma.

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Qi, F., Wu, J., Hao, D. et al. Comparative Studies on the Influences of Primary Emulsion Preparation on Properties of Uniform-Sized Exenatide-Loaded PLGA Microspheres. Pharm Res 31, 1566–1574 (2014). https://doi.org/10.1007/s11095-013-1262-6

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  • DOI: https://doi.org/10.1007/s11095-013-1262-6

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