开发一种新的同步 in vitro 溶解 - in situ perfusion 系统,作为研究固体口服配方在老鼠中吸收的潜在工具
Guo Chen1, Yumeng Zhu1, Qiaoqiao Wang1
1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No.103, Wenhua Road, Shenyang 110016, China.
概括
一个新的体外溶解- perfusion 系统 (SDPS) 有效评估药物性能,检测通用尼丁平片的质量差异错过了标准测试. 这种方法与体内数据有很强的相关性,可能减少动物试验.
科学领域:
- 药理动力学和药物输送方法
- 制药科学 制药科学
- 分析化学 分析化学
背景情况:
- 评估固体口服配方的体内性能对于药物的安全性和有效性至关重要.
- 传统的体外溶解试验可能无法充分区分具有微妙质量差异的配方.
- 需要先进的体外模型来更好地预测体内药物吸收.
研究的目的:
- 开发和验证一种新型的同步体外溶解- perfusion 系统 (SDPS),用于评估固体口服配方在老鼠中的性能.
- 为了比较SDPS与标准的体外溶解方法的区分能力,使用尼二平 (NTD) 仿制品.
- 评估SDPS对体内药物吸收的预测能力.
主要方法:
- 开发了一种同时体外溶解 - 现场 perfusion 系统 (SDPS).
- 分析了尼二平 (NTD) 参考列出的药物 (RLD) 和五种仿制产品.
- 采用标准溶解试验和开发的SDPS方法;使用自制NTD平板来评估SDPS的区分能力和预测性.
主要成果:
- SDPS检测到通用NTD产品和RLD之间的溶解概况在统计上有显著差异,标准溶解测试没有显示.
- 在SDPS实验中,A biexponential配方准确地描述了药物度概况,产生了参数 (kdis,ka),表明助剂不会影响NTD肠道吸收.
- SDPS数据显示,与鼠类体内药理动力学研究结果有很强的相关性 (R2 = 0.99).
结论:
- SDPS是检测药品质量的意想不到变化的有希望的工具,特别是在监管较少的市场.
- SDPS可以促进配方选,并可能减少用于预测口服固体剂型体内吸收行为的动物试验.
- 需要对仿制药的体内吸收性能进行进一步的研究.
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