State Key Laboratory of Bio-based Material and Green Papermaking (LBMP), Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.
Key Laboratory of Shandong Microbial Engineering, School of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.
Math Biosci Eng. 2022 May 31;19(8):8019-8034. doi: 10.3934/mbe.2022375.
The preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, a single polymer often does not bring significantly enhance the solubility or amorphous stability of a poorly water-soluble drug. We found an application of a unique and novel binary polymeric blend in the preparation of solid dispersions. The main purpose of this study is to optimize and evaluate resveratrol (Res) amorphous solid dispersions with a novel polymeric system of poly (vinyl pyrrolidone) (PVP) and carboxymethyl chitosan (CMCS). The influence of three different release factors, the ratio of CMCS to the polymer mixture (CMCS% = X), the ratio of Res to the polymer mixture (Res% = X) and the surfactant (Tween 80 = X), on the characteristics of released Res at various times (Q and Q) was investigated. The computer optimization and contour plots were used to predict the levels of the independent variables as X = 0.17, X = 0.10 and X = 2.94 for maximized responses of Q and Q. Fourier transform infrared spectroscopy (FTIR) results revealed that each polymer formed hydrogen bonds with Res. The solid performance and physical stability of the optimized ternary dispersions were studied with scanning electron microscopy (SEM), powder X-ray diffraction (XRD), modulated differential scanning calorimetry (MDSC) and dissolution testing. SEM, XRD and MDSC analysis demonstrated that the Res was amorphous, and MDSC showed no evidence of phase separation during storage. Dissolution testing indicated a more than fourfold increase in the apparent solubility of the optimized ternary dispersions, which maintained high solubility after 90 days. In our research, we used CMCS as a new carrier in combination with PVP, which not only improved the dissolution of Res but also had better stability.
使用聚合物制备无定形固体分散体是提高疏水性药物溶解度的常用制剂策略。然而，单一聚合物通常不能显著提高疏水性药物的溶解度或无定形稳定性。我们发现了一种独特新颖的二元聚合物共混物在制备固体分散体中的应用。本研究的主要目的是优化和评价具有新型聚合物系统聚乙烯吡咯烷酮（PVP）和羧甲基壳聚糖（CMCS）的白藜芦醇（Res）无定形固体分散体。研究了三个不同的释放因子，即 CMCS 与聚合物混合物的比例（CMCS%=X）、Res 与聚合物混合物的比例（Res%=X）和表面活性剂（Tween 80=X）对不同时间（Q 和 Q）释放的 Res 特性的影响。使用计算机优化和等高线图预测独立变量的水平为 X=0.17、X=0.10 和 X=2.94，以获得 Q 和 Q 的最大响应。傅里叶变换红外光谱（FTIR）结果表明，每种聚合物都与 Res 形成氢键。使用扫描电子显微镜（SEM）、粉末 X 射线衍射（XRD）、调制差示扫描量热法（MDSC）和溶解试验研究了优化的三元分散体的固体性能和物理稳定性。SEM、XRD 和 MDSC 分析表明 Res 为无定形，MDSC 在储存过程中没有相分离的证据。溶解试验表明，优化的三元分散体的表观溶解度增加了四倍以上，在 90 天后仍保持高溶解度。在我们的研究中，我们使用 CMCS 作为新的载体与 PVP 结合，不仅提高了 Res 的溶解性能，而且具有更好的稳定性。
