摘要
口服缓控释制剂作为药物递送系统的重要组成部分，近年来受到广泛关注。传统剂型难以满足临床对药物释放精准控制的需求，而新型口服缓控释制剂能够实现药物在体内的持续、稳定释放，提高治疗效果并减少不良反应。本研究旨在开发一种基于聚合物骨架的新型口服缓控释片剂，并对其药效进行系统评价。通过筛选不同分子量和取代度的羟丙甲纤维素（HPMC）作为基质材料，采用直接压片法制备缓控释片剂。利用体外溶出实验模拟胃肠道环境，考察药物释放行为；同时建立大鼠体内药动学模型，比较不同剂量组的血药浓度变化。结果显示，所制备的缓控释片剂具有良好的体外释药特性，释药过程符合Higuchi方程；体内实验表明该制剂能显著延长药物半衰期，降低峰谷波动，提高生物利用度。与市售普通片剂相比，新型缓控释制剂表现出更稳定的血药浓度曲线和平稳的药效维持时间。本研究创新性地引入了特定比例的复合辅料体系，优化了制剂工艺参数，为后续临床应用提供了理论依据和技术支持，有望成为慢性疾病长期治疗的理想选择。
关键词：口服缓控释制剂；羟丙甲纤维素；药物释放行为
Abstract
Oral extended-release formulations, as a critical component of drug delivery systems, have garnered significant attention in recent years. Conventional dosage forms often fail to meet the clinical demand for precise control of drug release, whereas novel oral extended-release formulations can achieve sustained and stable drug release in vivo, thereby enhancing therapeutic efficacy and reducing adverse reactions. This study aims to develop a novel polymer matrix-based oral extended-release tablet and systematically evaluate its pharmacological performance. Hydroxypropyl methylcellulose (HPMC) with varying molecular weights and degrees of substitution was selected as the matrix material, and tablets were prepared using the direct compression method. In vitro dissolution experiments were conducted to simulate gastrointestinal conditions and assess drug release behavior, while an in vivo pharmacokinetic model in rats was established to compare blood concentration changes across different dose groups. The results demonstrated that the prepared extended-release tablets exhibited favorable in vitro drug release characteristics, with the release process conforming to the Higuchi equation. In vivo experiments indicated that this formulation significantly prolonged the drug's half-life, reduced peak-to-trough fluctuations, and improved bioavailability. Compared to commercially available conventional tablets, the novel extended-release formulation showed more stable plasma concentration profiles and sustained therapeutic effects. This study innovatively introduced a specific ratio of composite excipient systems and optimized formulation parameters, providing theoretical basis and technical support for subsequent clinical applications, and holds promise as an ideal choice for long-term treatment of chronic diseases.
Keywords：Oral Controlled-Release Formulations; Hydroxypropyl Methylcellulose; Drug Release Behavior
目 录
摘要 I
Abstract II
一、绪论 1
(一) 研究背景与意义 1
(二) 国内外研究现状 1
(三) 研究方法与技术路线 2
二、新型缓控释制剂的设计原理 2
(一) 缓控释制剂的基本概念 2
(二) 设计原则与理论基础 3
(三) 关键影响因素分析 4
三、制备工艺与质量控制 4
(一) 制备技术选择 4
(二) 工艺参数优化 5
(三) 质量标准建立 6
四、药效评价体系构建 6
(一) 体外释放度测定 6
(二) 动物实验设计 7
(三) 临床前安全性评估 8
结 论 9
参考文献 10
口服缓控释制剂作为药物递送系统的重要组成部分，近年来受到广泛关注。传统剂型难以满足临床对药物释放精准控制的需求，而新型口服缓控释制剂能够实现药物在体内的持续、稳定释放，提高治疗效果并减少不良反应。本研究旨在开发一种基于聚合物骨架的新型口服缓控释片剂，并对其药效进行系统评价。通过筛选不同分子量和取代度的羟丙甲纤维素（HPMC）作为基质材料，采用直接压片法制备缓控释片剂。利用体外溶出实验模拟胃肠道环境，考察药物释放行为；同时建立大鼠体内药动学模型，比较不同剂量组的血药浓度变化。结果显示，所制备的缓控释片剂具有良好的体外释药特性，释药过程符合Higuchi方程；体内实验表明该制剂能显著延长药物半衰期，降低峰谷波动，提高生物利用度。与市售普通片剂相比，新型缓控释制剂表现出更稳定的血药浓度曲线和平稳的药效维持时间。本研究创新性地引入了特定比例的复合辅料体系，优化了制剂工艺参数，为后续临床应用提供了理论依据和技术支持，有望成为慢性疾病长期治疗的理想选择。
关键词：口服缓控释制剂；羟丙甲纤维素；药物释放行为
Abstract
Oral extended-release formulations, as a critical component of drug delivery systems, have garnered significant attention in recent years. Conventional dosage forms often fail to meet the clinical demand for precise control of drug release, whereas novel oral extended-release formulations can achieve sustained and stable drug release in vivo, thereby enhancing therapeutic efficacy and reducing adverse reactions. This study aims to develop a novel polymer matrix-based oral extended-release tablet and systematically evaluate its pharmacological performance. Hydroxypropyl methylcellulose (HPMC) with varying molecular weights and degrees of substitution was selected as the matrix material, and tablets were prepared using the direct compression method. In vitro dissolution experiments were conducted to simulate gastrointestinal conditions and assess drug release behavior, while an in vivo pharmacokinetic model in rats was established to compare blood concentration changes across different dose groups. The results demonstrated that the prepared extended-release tablets exhibited favorable in vitro drug release characteristics, with the release process conforming to the Higuchi equation. In vivo experiments indicated that this formulation significantly prolonged the drug's half-life, reduced peak-to-trough fluctuations, and improved bioavailability. Compared to commercially available conventional tablets, the novel extended-release formulation showed more stable plasma concentration profiles and sustained therapeutic effects. This study innovatively introduced a specific ratio of composite excipient systems and optimized formulation parameters, providing theoretical basis and technical support for subsequent clinical applications, and holds promise as an ideal choice for long-term treatment of chronic diseases.
Keywords：Oral Controlled-Release Formulations; Hydroxypropyl Methylcellulose; Drug Release Behavior
目 录
摘要 I
Abstract II
一、绪论 1
(一) 研究背景与意义 1
(二) 国内外研究现状 1
(三) 研究方法与技术路线 2
二、新型缓控释制剂的设计原理 2
(一) 缓控释制剂的基本概念 2
(二) 设计原则与理论基础 3
(三) 关键影响因素分析 4
三、制备工艺与质量控制 4
(一) 制备技术选择 4
(二) 工艺参数优化 5
(三) 质量标准建立 6
四、药效评价体系构建 6
(一) 体外释放度测定 6
(二) 动物实验设计 7
(三) 临床前安全性评估 8
结 论 9
参考文献 10
