摘 要
口腔崩解片（Orally Disintegrating Tablets, ODTs）因其快速崩解、便于吞咽和提高患者顺应性等优势，近年来在药物制剂领域受到广泛关注。然而，传统ODTs的制备工艺存在生产效率低、质量不稳定等问题，限制了其广泛应用。本研究旨在优化口腔崩解片的处方设计与制备工艺，以提升制剂性能并满足工业化生产需求。研究采用粉末直接压片法结合新型超速崩解剂，并通过响应面分析法对关键影响因素进行系统优化。实验中选取模型药物阿司匹林作为代表性活性成分，考察了不同辅料配比、压片压力及颗粒粒径等因素对片剂崩解时间、硬度和溶出度的影响。结果表明，通过引入复合崩解剂（交联聚维酮与低取代羟丙基纤维素的混合物），可显著缩短片剂崩解时间至15秒以内，同时保持良好的机械强度和药物释放特性。此外，基于单因素试验和Box-Behnken设计建立的数学模型成功预测了最优处方条件，验证试验结果显示理论值与实际值高度一致。本研究还开发了一种改良的连续化生产工艺，利用滚筒压缩技术替代传统湿法制粒，大幅提高了生产效率并降低了成本。最终制得的口腔崩解片具有优异的崩解性能、稳定的物理化学性质以及良好的口感体验。研究表明，优化后的处方设计与制备工艺不仅解决了传统ODTs存在的技术瓶颈，还为其他类似制剂的研发提供了重要参考，展现了良好的应用前景和产业化潜力。关键词：口腔崩解片；处方优化；超速崩解剂；连续化生产；响应面分析法
Abstract
Orally disintegrating tablets (ODTs) have garnered significant attention in the pharmaceutical formulation field due to their advantages of rapid disintegration, ease of swallowing, and improved patient compliance. However, traditional ODT manufacturing processes are limited by low production efficiency and unstable quality, hindering their widespread application. This study aimed to optimize the formulation design and preparation process of ODTs to enhance their performance and meet industrial production requirements. The research employed direct powder compression combined with a novel super-disintegrant and systematically optimized key influencing factors using response surface methodology. Aspirin was selected as the model drug to evaluate the effects of different excipient ratios, tablet compression pressures, and particle sizes on disintegration time, hardness, and dissolution profiles. Results demonstrated that incorporating a composite disintegrant (a mixture of cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose) significantly reduced disintegration time to less than 15 seconds while maintaining excellent mechanical strength and drug release characteristics. Furthermore, a mathematical model established based on single-factor experiments and Box-Behnken design successfully predicted optimal formulation conditions, with validation trials showing high consistency between theoretical and actual values. This study also developed an improved continuous manufacturing process by substituting traditional wet granulation with roller compaction technology, substantially enhancing production efficiency and reducing costs. The resulting ODTs exhibited superior disintegration properties, stable physicochemical characteristics, and favorable taste experience. This research not only addressed the technical bottlenecks of conventional ODTs but also provided valuable references for the development of similar formulations, demonstrating promising application prospects and industrialization potential..
Key Words：Oral Disintegrating Tablet；Formula Optimization；Superdisintegrant；Continuous Manufacturing；Response Surface Methodology
目 录
摘 要 I
Abstract II
第1章 绪论 2
1.1 口腔崩解片研究背景与意义 2
1.2 口腔崩解片处方设计与制备工艺的研究现状 2
1.3 本文研究方法与技术路线 3
第2章 口腔崩解片处方设计的关键因素分析 5
2.1 处方设计中的辅料选择策略 5
2.2 崩解剂对口腔崩解片性能的影响 5
2.3 黏合剂在处方设计中的作用机制 6
2.4 润滑剂与填充剂的优化配置 7
第3章 口腔崩解片制备工艺改进研究 8
3.1 制备工艺改进的基本原则 8
3.1.1 工艺改进的目标设定 8
3.1.2 关键工艺参数的筛选 8
3.1.3 工艺改进的技术路径 9
3.1.4 工艺优化的评价标准 9
3.2 直接压片法的应用与改进 9
3.2.1 直接压片的优势分析 10
3.2.2 压片过程中常见问题及解决策略 10
3.2.3 压片力对片剂质量的影响 10
3.2.4 改进后的直接压片效果评估 11
3.3 冷冻干燥法制备工艺优化 11
3.3.1 冷冻干燥法的特点与适用范围 11
3.3.2 冻干过程中的关键控制点 12
3.3.3 冻干参数对片剂性能的影响 12
3.3.4 冷冻干燥法的改进措施 13
第4章 口腔崩解片质量评价与稳定性研究 14
4.1 质量评价体系的构建 14
4.1.1 片剂外观质量检测方法 14
4.1.2 崩解时间的测定与分析 14
4.1.3 含量均匀性的评估方法 15
4.1.4 溶出度测试及其影响因素 15
4.2 稳定性研究的设计与实施 15
4.2.1 稳定性试验的基本要求 16
4.2.2 影响稳定性的主要因素分析 16
4.2.3 加速试验条件的选择与结果解读 17
4.2.4 长期稳定性试验的数据分析 17
4.3 质量改进措施与建议 17
4.3.1 针对质量问题的解决方案 18
4.3.2 提高产品质量的工艺调整策略 18
4.3.3 质量控制标准的完善方向 18
结 论 19
参考文献 20
致 谢 21
