Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Korea.
College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 15588, Korea.
Int J Mol Sci. 2022 Aug 22;23(16):9491. doi: 10.3390/ijms23169491.
The purpose of this study was to investigate the efficacy of hydrophilic polymers in a solid dispersion formulation in improving the solubility and dissolution rate of rivaroxaban (RXB), a poorly soluble drug. The developed solid dispersion consisted of two components, a drug and a polymer, and the drug was dispersed as amorphous particles in a polymer matrix using the spray drying method. Polymeric solid dispersions were evaluated using solubility tests, in vitro dissolution tests, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and particle size distribution analysis. To maximize physical stability against crystallization and improve the solubility and dissolution of RXB, it is important to select the appropriate polymer type and the optimal ratio of the polymer to the drug. The optimized polyvinyl alcohol (PVA)-based (1/0.5, /) and gelatin-based (1/5, /) solid dispersion formulations showed 6.3 and 3.6 times higher drug solubilities than pure RXB powder, respectively, and the final dissolution rate was improved by approximately 1.5 times. Scanning electron microscopy and particle size distribution analyses confirmed that the gelatin-based solid dispersion was smaller and more spherical than the PVA-based solid dispersion, suggesting that the gelatin-based solid dispersion had a faster initial dissolution rate. Differential scanning calorimetry and powder X-ray diffraction analyses confirmed that RXB had successfully changed from a crystalline form to an amorphous form, contributing to the improvement in its solubility and dissolution rate. This study provides a strategy for selecting suitable polymers for the development of amorphous polymer solid dispersions that can overcome precipitation during dissolution and stabilization of the amorphous state. In addition, the selected polymer solid dispersion improved the drug solubility and dissolution rate of RXB, a poorly soluble drug, and may be used as a promising drug delivery system.
本研究旨在考察亲水性聚合物在固体分散体配方中改善利伐沙班（RXB）溶解度和溶出速率的效果。所开发的固体分散体由两部分组成，即药物和聚合物，药物采用喷雾干燥法以无定形颗粒形式分散在聚合物基质中。采用溶解度试验、体外溶出试验、粉末 X 射线衍射、差示扫描量热法、扫描电子显微镜和粒径分布分析对聚合物固体分散体进行了评价。为了最大限度地提高抗结晶的物理稳定性并提高 RXB 的溶解度和溶出度，选择合适的聚合物类型和聚合物与药物的最佳比例非常重要。优化的聚乙烯醇（PVA）（1/0.5，/）和明胶（1/5，/）基固体分散体制剂的药物溶解度分别比纯 RXB 粉末高 6.3 倍和 3.6 倍，最终溶出速率提高了约 1.5 倍。扫描电子显微镜和粒径分布分析证实，明胶基固体分散体比 PVA 基固体分散体更小且更球形，表明明胶基固体分散体具有更快的初始溶出速率。差示扫描量热法和粉末 X 射线衍射分析证实，RXB 已成功从结晶形式转变为无定形形式，这有助于提高其溶解度和溶出速率。本研究为开发可克服溶解过程中沉淀和稳定无定形状态的适用于制备无定形聚合物固体分散体的合适聚合物提供了一种策略。此外，所选聚合物固体分散体提高了难溶性药物 RXB 的药物溶解度和溶出速率，可作为有前途的药物传递系统。
