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基于 PEG/PCL 共混物的吡喹酮植入剂的体内外评价。

In vitro and in vivo evaluation of praziquantel loaded implants based on PEG/PCL blends.

机构信息

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

出版信息

Int J Pharm. 2010 Mar 15;387(1-2):129-38. doi: 10.1016/j.ijpharm.2009.12.010. Epub 2009 Dec 18.

Abstract

In the present study, a series of praziquantel (PZQ) loaded implants based on PEG/PCL blends are fabricated by a combination of twin-screw mixing and hot-melt extrusion. In vitro drug release from these implants and the performance of the implants after implantation in rats are evaluated. XRD and DSC analysis results exhibit each component in the implants is mainly in its crystalline state. Dissolution test shows that the higher PEG content there is in the implants, the faster the drug will be released. Interestingly, PEG release from all implants is far faster than PZQ release, and complete PEG release occurs in 72 h. SEM result displays that after the in vitro drug release test, the cross-sections of implants with low PEG contents (0-5%) primarily consist of discrete pores; while those of implants with high PEG contents (10-30%) consist of interconnected pores or channels. The fitting results of drug release data with kinetic models reveal that PZQ release is governed by diffusion. After implantation, drug release becomes more moderate compared with in vitro drug release, and it tends to follow zero-order in the later stage. These results suggest that changing the composition of the PEG/PCL blends is an effective tool to adjust in vitro/in vivo drug release from the implants.

摘要

在本研究中,通过双螺杆混合和热熔挤出相结合的方法制备了一系列基于 PEG/PCL 共混物的吡喹酮(PZQ)负载植入物。评估了这些植入物的体外药物释放和在大鼠体内植入后的性能。XRD 和 DSC 分析结果表明,植入物中的每个成分主要处于结晶状态。溶出试验表明,植入物中 PEG 含量越高,药物释放速度越快。有趣的是,所有植入物中 PEG 的释放速度都远远快于 PZQ 的释放速度,PEG 在 72 小时内完全释放。SEM 结果显示,在体外药物释放试验后,PEG 含量低(0-5%)的植入物的横截面主要由离散的孔组成;而 PEG 含量高(10-30%)的植入物的横截面由相互连接的孔或通道组成。药物释放数据与动力学模型的拟合结果表明,PZQ 的释放由扩散控制。植入后,与体外药物释放相比,药物释放变得更加温和,在后期趋于遵循零级。这些结果表明,改变 PEG/PCL 共混物的组成是调节植入物中体外/体内药物释放的有效工具。

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