College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-gu, Daegu, 42601, Republic of Korea.
Center for Forensic Pharmaceutical Sciences, 1095 Dalgubeol-daero, Dalseo-gu, Daegu, 42601, Republic of Korea.
Arch Pharm Res. 2022 Jan;45(1):29-37. doi: 10.1007/s12272-022-01368-4. Epub 2022 Feb 7.
Improving the aqueous solubility of poorly soluble compounds have been a major issue in the pharmaceutical industry. In the present study, binary amorphous solid dispersions (SDs) of Coenzyme Q10 (CoQ), a biopharmaceutics classification system (BCS) II compound and Soluplus were prepared to enhance the solubility and pharmacokinetic properties compared to crystalline CoQ. SDs were prepared with different ratios of CoQ and Soluplus (1:3, 1:5, and 1:7) using spray drying technology, and the physicochemical properties of the SDs were evaluated. X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy suggested the conversion of the crystalline form of CoQ to a binary amorphous system in the SDs. Fourier transform infrared spectroscopy revealed no potential interactions between CoQ and Soluplus. The solubility of the optimal SD formulation (SD 1:7) was approximately 9000-fold higher than that of crystalline CoQ and the increment was Soluplus concentration dependent. As a result, optimized SD 1:7 also showed significantly enhanced dissolution rate where maximum drug release was observed within 30 min in two different dissolution media. Moreover, in contrast to crystalline CoQ CoQ SDs showed improved pharmacokinetic parameters. Thus, the SD 1:7 formulation is expected to improve biopharmaceutical properties and therapeutic efficacy of CoQ.
提高难溶性化合物的水溶性一直是制药行业的一个主要问题。在本研究中,制备了辅酶 Q10(CoQ)的二元无定形固体分散体(SD),CoQ 是生物药剂学分类系统(BCS)II 类化合物和 Soluplus,以提高其溶解度和药代动力学性质,与结晶 CoQ 相比。采用喷雾干燥技术,用不同比例的 CoQ 和 Soluplus(1:3、1:5 和 1:7)制备 SD,并对 SD 的理化性质进行评价。X 射线粉末衍射、差示扫描量热法和扫描电子显微镜表明,SD 中 CoQ 的晶型转化为二元无定形体系。傅里叶变换红外光谱显示 CoQ 和 Soluplus 之间没有潜在的相互作用。最佳 SD 配方(SD 1:7)的溶解度约为结晶 CoQ 的 9000 倍,且增量与 Soluplus 浓度有关。因此,优化后的 SD 1:7 还表现出显著提高的溶解速率,在两种不同的溶解介质中,在 30 分钟内观察到最大药物释放。此外,与结晶 CoQ 相比,CoQ SD 显示出改善的药代动力学参数。因此,SD 1:7 配方有望改善 CoQ 的生物药剂学性质和治疗效果。