摘要
随着新型药物递送系统的快速发展，口服固体制剂的体内外相关性研究已成为确保药品质量和疗效的关键环节。本研究旨在建立一种高效、可靠的体内外相关性模型，以评估新型口服固体制剂在不同生理条件下的吸收行为和药代动力学特征。为此，采用多学科交叉方法，结合体外溶出实验与体内药动学研究，选取多种具有代表性的药物制剂作为研究对象，通过优化溶出介质和搅拌速率等参数，模拟胃肠道环境的复杂变化。同时，引入先进的数学建模技术，构建非线性回归分析模型，以提高预测精度和适用范围。研究结果表明，所建立的模型能够准确反映制剂在人体内的吸收过程，并成功揭示了关键辅料对药物释放行为的影响机制。此外，本研究首次提出了一种基于个体化生理参数的动态调整策略，显著提升了模型的普适性和临床指导价值。这一创新方法不仅为新型口服固体制剂的研发提供了重要工具，也为个性化药物治疗奠定了理论基础，具有重要的学术意义和应用前景。
关键词：体内外相关性；口服固体制剂；数学建模；个性化生理参数；药物释放行为
Abstract
With the rapid development of novel drug delivery systems, the in vitro-in vivo correlation (IVIVC) study of oral solid dosage forms has become a critical step in ensuring drug quality and efficacy. This research aims to establish an efficient and reliable IVIVC model for evaluating the absorption behavior and pharmacokinetic characteristics of novel oral solid formulations under various physiological conditions. A multidisciplinary approach was employed, integrating in vitro dissolution experiments with in vivo pharmacokinetic studies. Multiple representative drug formulations were selected as research subjects, and parameters such as dissolution media and stirring rates were optimized to simulate the complex variations of the gastrointestinal environment. Meanwhile, advanced mathematical modeling techniques were introduced to construct nonlinear regression analysis models, thereby enhancing prediction accuracy and applicability. The results demonstrate that the established model accurately reflects the absorption process of formulations in the human body and successfully elucidates the impact mechanism of key excipients on drug release behavior. Furthermore, this study proposes for the first time a dynamic adjustment strategy based on individualized physiological parameters, significantly improving the model's universality and clinical guidance value. This innovative method not only provides an essential tool for the development of novel oral solid formulations but also lays a theoretical foundation for personalized drug therapy, holding significant academic importance and application potential.
Keywords：In Vivo In Vitro Correlation; Oral Solid Dosage Forms; Mathematical Modeling; Personalized Physiological Parameters; Drug Release Behavior
目 录
摘要 I
Abstract II
一、绪论 1
(一) 新型口服固体制剂的研究背景 1
(二) 体内外相关性研究的意义与价值 1
(三) 国内外研究现状分析 1
(四) 本文研究方法与技术路线 2
二、体内外相关性的理论基础 2
(一) 体内外相关性的定义与分类 2
(二) 影响体内外相关性的关键因素 3
(三) 数学模型在相关性研究中的应用 3
(四) 理论基础对研究的指导作用 4
三、新型口服固体制剂的体内行为研究 4
(一) 制剂吸收机制与动力学分析 4
(二) 生物利用度与药代动力学评价 5
(三) 不同制剂配方的体内表现差异 5
(四) 体内实验数据的采集与处理 6
四、新型口服固体制剂的体外特性研究 6
(一) 体外溶出度测试方法优化 6
(二) 溶出曲线与释放行为分析 7
(三) 体外特性与制剂质量的关系 7
(四) 体外实验结果的可靠性验证 8
结 论 9
参考文献 10
