摘要
药物晶型作为影响药物理化性质和生物利用度的关键因素，其研究在药物开发中具有重要意义。本研究旨在探讨不同晶型对药物溶解度、稳定性及吸收行为的影响，并提出有效的晶型调控策略以优化药物的生物利用度。通过系统分析多种药物模型的晶体结构特性，结合体外溶解实验与体内药代动力学研究，揭示了晶型差异对药物吸收过程的作用机制。研究发现，无定形晶型通常表现出更高的溶解度和更快的吸收速率，但其物理化学稳定性较差；而特定有序晶型虽溶解性能较低，却可通过共晶、盐型转化或纳米晶技术显著改善其生物利用度。基于此，本文提出了以晶体工程为核心的综合调控方法，包括溶剂化处理、共晶设计及表面修饰等手段，有效解决了部分低溶解性药物的吸收限制问题。该研究不仅为晶型筛选提供了理论依据，还为优化药物制剂设计开辟了新途径，其创新点在于将晶体结构特性与生物利用度提升策略有机结合，为个性化药物研发奠定了基础。研究成果对提高药物疗效、降低给药剂量及减少副作用具有重要应用价值。
关键词：药物晶型；生物利用度；晶型调控；无定形晶型；共晶设计
Abstract
Pharmaceutical polymorphs play a critical role in influencing the physicochemical properties and bioavailability of drugs, making their study highly significant in drug development. This research aims to investigate the impact of different polymorphs on drug solubility, stability, and absorption behavior while proposing effective strategies for polymorph control to optimize drug bioavailability. By systematically analyzing the crystal structure characteristics of multiple drug models and integrating in vitro dissolution experiments with in vivo pharmacokinetic studies, the mechanisms by which polymorphic differences affect drug absorption processes were elucidated. The findings indicate that amorphous forms generally exhibit higher solubility and faster absorption rates but possess inferior physicochemical stability. In contrast, certain ordered crystalline forms, despite lower solubility performance, can significantly enhance bioavailability through techniques such as cocrystallization, salt form conversion, or nanocrystallization. Based on these insights, this paper proposes an integrated modulation approach centered on crystal engineering, including solvent treatment, cocrystal design, and surface modification, effectively addressing absorption limitations for some poorly soluble drugs. This study not only provides a theoretical basis for polymorph screening but also opens new avenues for optimizing drug formulation design. Its innovation lies in the organic combination of crystal structure characteristics with strategies for enhancing bioavailability, laying a foundation for personalized drug development. The research outcomes hold significant application value in improving drug efficacy, reducing dosing requirements, and minimizing side effects.
Keywords：Drug Polymorph; Bioavailability; Polymorph Control; Amorphous Form; Cocrystal Design
目 录
摘要 I
Abstract II
一、绪论 1
(一) 药物晶型与生物利用度的研究背景 1
(二) 国内外研究现状与挑战 1
(三) 研究方法与技术路线 2
二、药物晶型对溶解度的影响分析 2
(一) 晶型结构与溶解性能的关系 2
(二) 不同晶型的热力学稳定性探讨 3
(三) 晶型转变对溶解度的影响机制 3
三、药物晶型对吸收过程的作用机制 4
(一) 晶型特性对胃肠吸收的影响 4
(二) 生物膜渗透性与晶型关系研究 4
(三) 晶型对药物体内分布的影响 5
四、药物晶型调控策略及其优化研究 5
(一) 晶型筛选与设计方法研究 5
(二) 制备工艺对晶型控制的影响 6
(三) 晶型稳定性评估与优化策略 7
结 论 8
参考文献 9
