摘要
固体口服制剂的溶出度和生物利用度是影响药物疗效的关键因素，尤其对于难溶性药物，其处方优化具有重要意义。本研究旨在通过系统化的处方设计与工艺改进，提升固体口服制剂的溶出性能。研究选取了三种典型难溶性药物作为模型，采用质量源于设计（QbD）理念指导实验设计，并结合响应面分析法（RSM）对关键辅料比例、制粒工艺参数及压片条件进行优化。结果表明，通过调整表面活性剂种类与用量、引入纳米晶技术以及优化颗粒粒径分布，可显著改善药物的溶出特性。此外，研究还开发了一种新型复合崩解剂，其在低用量下即可实现快速崩解效果，进一步促进了药物释放。与传统处方相比，优化后的制剂在模拟胃肠道环境下表现出更高的溶出速率和累计溶出量，且工艺稳定性得到显著提升。本研究的创新点在于将多学科技术手段整合应用于处方优化过程，为难溶性药物的开发提供了新思路，同时为工业规模化生产奠定了理论基础。研究成果不仅有助于提高药物疗效，还为个性化制剂设计提供了参考方案。
关键词：难溶性药物；处方优化；质量源于设计（QbD）；响应面分析法（RSM）；复合崩解剂
Abstract
The dissolution and bioavailability of solid oral formulations are critical factors affecting drug efficacy, particularly for poorly soluble drugs, where formulation optimization plays a significant role. This study aims to enhance the dissolution performance of solid oral formulations through systematic design and process improvement. Three typical poorly soluble drugs were selected as models, and the Quality by Design (QbD) concept was employed to guide experimental design. Response Surface Methodology (RSM) was utilized to optimize the proportions of key excipients, granulation process parameters, and tablet compression conditions. The results indicate that adjusting the type and amount of surfactants, incorporating nanocrystal technology, and optimizing particle size distribution can significantly improve drug dissolution characteristics. Additionally, a novel composite disintegrant was developed, which achieves rapid disintegration even at low dosage levels, further promoting drug release. Compared with traditional formulations, the optimized formulations exhibit higher dissolution rates and cumulative dissolution amounts under simulated gastrointestinal conditions, along with significantly improved process stability. The innovation of this study lies in the integration of multidisciplinary technical approaches into the formulation optimization process, providing new insights for the development of poorly soluble drugs and laying a theoretical foundation for industrial-scale production. The research not only contributes to enhancing drug efficacy but also offers reference solutions for personalized formulation design.
Keywords：Poorly Soluble Drugs; Formulation Optimization; Quality By Design (QbD); Response Surface Methodology (RSM); Composite Disintegrant
目 录
摘要 I
Abstract II
一、绪论 1
(一) 固体口服制剂研究背景与意义 1
(二) 处方优化与溶出度提升的研究现状 1
(三) 本文研究方法与技术路线 2
二、处方设计对溶出行为的影响 2
(一) 关键辅料选择与作用机制 2
(二) 制剂工艺对溶出度的影响分析 3
(三) 处方筛选与优化策略 3
三、溶出度提升的技术手段 4
(一) 微粉化技术的应用与效果评估 4
(二) 固体分散体的制备与性能优化 4
(三) 新型载体材料的引入与评价 5
四、处方优化的实际案例研究 6
(一) 典型药物的处方优化实例 6
(二) 溶出曲线对比与数据分析 6
(三) 工艺参数调整与质量控制 7
结 论 8
参考文献 9
