School of Pharmacy & Health Professions, Creighton University, Omaha, NE 68178, United States.
School of Pharmacy, MCPHS University, Boston, MA 20115, United States.
Eur J Pharm Sci. 2015 Apr 25;71:12-24. doi: 10.1016/j.ejps.2015.02.003. Epub 2015 Feb 14.
Curcumin (CUR) was used as a poorly soluble drug whereas polyvinyl pyrrolidone K90 (PVP), Eudragit EPO (EPO), hydroxypropyl methylcellulose E5 (HPMC) and polyethylene glycol 8000 (PEG) were used as hydrophilic polymers. CUR polymer miscibility was evaluated by solubility parameter, melting point depression and glass transition temperature (Tg) measurements. Molecular interactions between CUR and polymers were determined by Fourier-transform infrared spectroscopy (FTIR) and Raman. Amorphous solid dispersions were prepared with CUR-polymer ratio of 70:30 (w/w) by solvent evaporation technique and were evaluated for dissolution enhancement using USP II method. Physical states of solid dispersions were characterized by X-ray diffraction (XRD) whereas thermal behaviors were investigated using modulated differential scanning calorimetry (MDSC). CUR-EPO system showed good miscibility through all the approaches, whereas immiscibility was found in other CUR-polymer systems. CUR-EPO and CUR-HPMC systems showed significant molecular interactions whereas CUR-PVP and CUR-PEG showed no molecular interactions. All solid dispersions showed significant dissolution enhancement with CUR-EPO showing highest dissolution rate during first 1h whereas CUR-HPMC was effective in maintaining high CUR concentrations for 6h. The study highlights the importance of investigating and correlating drug polymer miscibility and molecular interactions by various approaches for successful formulation of amorphous solid dispersions.
姜黄素（CUR）被用作难溶性药物，而聚乙烯吡咯烷酮 K90（PVP）、Eudragit EPO（EPO）、羟丙基甲基纤维素 E5（HPMC）和聚乙二醇 8000（PEG）则被用作亲水性聚合物。通过溶解度参数、熔点降低和玻璃化转变温度（Tg）测量评估 CUR 聚合物的混溶性。通过傅里叶变换红外光谱（FTIR）和拉曼确定 CUR 和聚合物之间的分子相互作用。通过溶剂蒸发技术将 CUR-聚合物比例为 70:30（w/w）制备无定形固体分散体，并使用 USP II 方法评估其溶解增强效果。通过 X 射线衍射（XRD）对固体分散体的物理状态进行表征，而通过调制差示扫描量热法（MDSC）研究其热行为。通过所有方法均表明 CUR-EPO 系统具有良好的混溶性，而其他 CUR-聚合物系统则表现出不混溶性。CUR-EPO 和 CUR-HPMC 系统显示出显著的分子相互作用，而 CUR-PVP 和 CUR-PEG 则没有显示出分子相互作用。所有固体分散体均显示出显著的溶解增强效果，其中 CUR-EPO 在最初 1 小时内显示出最高的溶解速率，而 CUR-HPMC 则能有效维持 6 小时内的高 CUR 浓度。该研究强调了通过各种方法研究和关联药物聚合物混溶性和分子相互作用对于成功制备无定形固体分散体的重要性。
