Paul Sagar Kumar, Kumari Dunesh, Destino Joel, Chauhan Harsh
Pharmaceutical Professional, Watertown, Massachusetts, USA.
Principal Scientist, Apeloa Pharmaceutical, Billerica, Massachusetts, USA.
AAPS PharmSciTech. 2025 May 6;26(5):125. doi: 10.1208/s12249-025-03123-6.
Ternary amorphous solid dispersions (TASD) are a three-component system that incorporates at least one drug in an amorphous form, offering potential advantages over conventional binary amorphous solid dispersions (ASD). This study aimed to design, characterize, and evaluate a stable and soluble high drug-loaded TASD combining two poorly water-soluble drugs, curcumin (CUR) and resveratrol (RES), with a hydrophilic polymer. Polymer screening studies, including miscibility, crystallization tendency, Flory-Huggins interaction parameter, and solubility parameter, were complemented by advanced techniques such as crystallization kinetics and molecular interaction analysis to assess drug-polymer interactions and amorphous stability. After selecting the optimal polymer, TASDs were prepared by rotary evaporation. Pure drugs, physical mixtures, binary, and ternary ASDs were characterized using X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy, and Raman spectroscopy. In-vitro dissolution under non-sink conditions was performed using a USP-II apparatus, and centrifuged samples were analyzed by UV-Vis spectroscopy. Long-term physical stability was assessed over 12 months at room temperature. Eudragit EPO was identified as the optimal polymer among EPO, HPMCAS, and S100. The resulting high drug-loaded (50% w/w) TASD was amorphous, exhibiting a single glass transition temperature (Tg) with strong drug-polymer interactions. In dissolution studies, the 50% drug-loaded TASD showed a ~ 197-fold and ~ fourfold increase in dissolved CUR and RES, respectively, compared to the crystalline drugs in the physical mixture after 1 h in acidic condition. Despite a lower RES release, it was still twice the release from binary ASDs. The TASD formulation remained physically amorphous for 12 months at room temperature storage.
三元无定形固体分散体（TASD）是一种三组分体系，其中包含至少一种无定形形式的药物，与传统的二元无定形固体分散体（ASD）相比具有潜在优势。本研究旨在设计、表征和评估一种稳定且可溶的高载药量TASD，该TASD将两种难溶性药物姜黄素（CUR）和白藜芦醇（RES）与一种亲水性聚合物结合。通过结晶动力学和分子相互作用分析等先进技术对聚合物筛选研究进行补充，包括混溶性、结晶趋势、弗洛里-哈金斯相互作用参数和溶解度参数，以评估药物-聚合物相互作用和无定形稳定性。选择最佳聚合物后，通过旋转蒸发制备TASD。使用X射线衍射（XRD）、差示扫描量热法（DSC）、热重分析（TGA）、傅里叶变换红外（FTIR）光谱和拉曼光谱对纯药物、物理混合物、二元和三元ASD进行表征。在非漏槽条件下使用USP-II装置进行体外溶出，并通过紫外-可见光谱对离心后的样品进行分析。在室温下评估12个月的长期物理稳定性。在EPO、HPMCAS和S100中，Eudragit EPO被确定为最佳聚合物。所得的高载药量（50% w/w）TASD为无定形，表现出单一的玻璃化转变温度（Tg），且药物-聚合物相互作用强烈。在溶出研究中，与物理混合物中的结晶药物相比，50%载药量的TASD在酸性条件下1小时后溶解的CUR和RES分别增加了约197倍和约4倍。尽管RES释放较低，但仍是二元ASD释放量的两倍。TASD制剂在室温储存12个月期间保持物理无定形状态。
