Huang Hua, Zhang Yong, Liu Yao, Guo Yufei, Hu Chunhui
Medical College, Qinghai University, Xining 810001, China.
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810001, China.
Pharmaceutics. 2023 Oct 19;15(10):2493. doi: 10.3390/pharmaceutics15102493.
Crystalline solid dispersions (CSDs) represent a thermodynamically stable system capable of effectively reducing the crystallite size of drugs, thereby enhancing their solubility and bioavailability. This study uses flavonoid drugs with the same core structures but varying numbers of hydroxyl groups as model drugs and poloxamer 188 as a carrier to explore the intrinsic relationships between drug-polymer interactions, crystallite size, and in vitro dissolution behavior in CSDs. Initially, we investigate the interactions between flavonoid drugs and P188 by calculating Hansen solubility parameters, determination of Flory-Huggins interaction parameters, and other methods. Subsequently, we explore the crystallization kinetics of flavonoid drugs and P188 in CSD systems using polarized optical microscopy and powder X-ray diffraction. We monitor the domain size and crystallite size of flavonoids in CSDs through powder X-ray diffraction and a laser-particle-size analyzer. Finally, we validate the relationship between crystallite size and in vitro dissolution behavior through powder dissolution. The results demonstrate that, as the number of hydroxyl groups increases, the interactions between drugs and polymers become stronger, making drug crystallization in the CSD system less likely. Consequently, reductions in crystalline domain size and crystallite size become more pronounced, leading to a more significant enhancement in drug dissolution.
结晶固体分散体（CSDs）是一种热力学稳定体系，能够有效减小药物的微晶尺寸，从而提高其溶解度和生物利用度。本研究以具有相同核心结构但羟基数量不同的黄酮类药物为模型药物，泊洛沙姆188为载体，探讨CSDs中药物 - 聚合物相互作用、微晶尺寸与体外溶出行为之间的内在关系。首先，我们通过计算汉森溶解度参数、测定弗洛里 - 哈金斯相互作用参数等方法研究黄酮类药物与P188之间的相互作用。随后，我们使用偏光显微镜和粉末X射线衍射研究CSD体系中黄酮类药物和P188的结晶动力学。我们通过粉末X射线衍射和激光粒度分析仪监测CSDs中黄酮类化合物的畴尺寸和微晶尺寸。最后，我们通过粉末溶出度验证微晶尺寸与体外溶出行为之间的关系。结果表明，随着羟基数量的增加，药物与聚合物之间的相互作用增强，使得CSD体系中药物结晶的可能性降低。因此，结晶域尺寸和微晶尺寸的减小变得更加明显，导致药物溶出度有更显著的提高。
