APT011缓释微球的制备及体外评价

doi:10.5246/jcps.2020.08.052

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (8): 554-563.DOI: 10.5246/jcps.2020.08.052

APT011缓释微球的制备及体外评价

李承群^1,2, 牛霞², 牟家慧², 王晓梅², 苏瑾^1*, 李桂玲^2*

1. 佳木斯大学, 黑龙江佳木斯 154007
2. 中国医学科学院北京协和医学院医药生物技术研究所, 北京 100050

收稿日期:2020-03-12 修回日期:2020-04-19 出版日期:2020-08-31 发布日期:2020-05-18
通讯作者: Tel.: +86-13803659063; +86-10-67022156, E-mail: liguiling1999@163.com; sj0129@163.com
基金资助:
National Science & Technology Major Project “Key New Drug Creation and Manufacturing” (Grant No. 2019ZX09201001-003-007).

Preparation and in vitro evaluation of APT011-loaded sustained-release microspheres

Chengqun Li^1,2, Xia Niu², Jiahui Mu², Xiaomei Wang², Jin Su^1*, Guiling Li^2*

1. Department of Pharmacy, Jiamusi University, Jiamusi 154007, China
2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China

Received:2020-03-12 Revised:2020-04-19 Online:2020-08-31 Published:2020-05-18
Contact: Tel.: +86-13803659063; +86-10-67022156, E-mail: liguiling1999@163.com; sj0129@163.com
Supported by:
National Science & Technology Major Project “Key New Drug Creation and Manufacturing” (Grant No. 2019ZX09201001-003-007).

摘要/Abstract

摘要：

本研究目的在于制备新的神经激肽-1受体拮抗剂—APT011缓释注射微球, 并对其理化性质、体外释放及初步稳定性进行评价。首先采用W/O/W复乳溶剂挥发法制备载药微球, 并用正交设计实验优化处方工艺。显微观察结果显示该载药微球为球形, 圆整度好; 平均粒径为90 μm, 粒径分布均匀; 粉末X-衍射结果表明APT011在微球内部以无定型形式存在; DSC结果表明药物APT011与空白微球无明显相互作用。此外, 载APT011微球具有明显的缓释效果, 可持续释放2个月。初步稳定性结果表明在40 °C和光照条件下, 微球的载药量与突释效应没有明显改变。上述结果说明, 载APT011微球具有优良的理化性质、缓释特性和初步稳定性, 具有进入临床的潜力。

关键词: PLGA, 微球, 处方工艺, 体外评价, 初步稳定性

Abstract:

In the present study, we aimed to prepare sustained-release microspheres for injection of neurokinin-1 (NK-1) receptor antagonist APT011, and to evaluate their physicochemical properties, in vitro sustained-release effect and preliminary stability. APT011-loaded sustained-release microspheres were prepared using W/O/W double emulsion-solvent evaporation technique. The L9 (3⁴) orthogonal experiment was used to optimize the APT011 sustained-release microsphere formulation. Microscope photographs showed that APT011-loaded microspheres were spherical, and the particle size was ~90 μm with uniform size distribution. XRD results indicated that APT011 existed in the microspheres in an amorphous form. DSC results showed that there was no significant interaction between APT011 and blank microspheres. APT011-loaded microspheres had a significant sustained-release effect, which maintained release for at least 2 months. Preliminary study results indicated that the loading content and release percentage at 0.5 h were not markedly altered below 40 °C and under high lighting condition. APT011-loaded microspheres prepared in our study exhibited excellent physicochemical properties and sustained-release characteristics and preliminary stability, demonstrating real potential for the clinical practice.

Key words: PLGA, Microsphere, Prescription technology, In vitro evaluation, Preliminary stability

中图分类号:

R943

Supporting:

李承群, 牛霞, 牟家慧, 王晓梅, 苏瑾, 李桂玲. APT011缓释微球的制备及体外评价[J]. 中国药学(英文版), 2020, 29(8): 554-563.

Chengqun Li, Xia Niu, Jiahui Mu, Xiaomei Wang, Jin Su, Guiling Li. Preparation and in vitro evaluation of APT011-loaded sustained-release microspheres[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(8): 554-563.

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APT011缓释微球的制备及体外评价

Preparation and in vitro evaluation of APT011-loaded sustained-release microspheres

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