Solomon Cristina, Anuța Valentina, Sarbu Iulian, Ozon Emma Adriana, Musuc Adina Magdalena, Bratan Veronica, Rusu Adriana, Surdu Vasile-Adrian, Croitoru Cătălin, Chandak Abhay, Gavriloaia Roxana Mariuca, Balaci Teodora Dalila, Niță Denisa Teodora, Mitu Mirela Adriana
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia St., 020956 Bucharest, Romania.
Innovative Therapeutic Structures Research and Development Centre (InnoTher), "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania.
Pharmaceuticals (Basel). 2025 May 22;18(6):761. doi: 10.3390/ph18060761.
: Rivaroxaban, an oral anticoagulant, shows poor aqueous solubility, posing significant challenges to its bioavailability and therapeutic efficiency. The present study investigates the improvement of rivaroxaban's solubility through the formation of different inclusion complexes with three cyclodextrin derivatives, such as β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by lyophilization in order to stabilize the complexes and improve dissolution characteristics of rivaroxaban. : The physicochemical properties of the individual compounds and the three lyophilized complexes were analysed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). : FTIR spectra confirmed the formation of non-covalent interactions between rivaroxaban and the cyclodextrins, suggesting successful encapsulation into cyclodextrin cavity. SEM images revealed a significant morphological transformation from the crystalline structure of pure rivaroxaban and cyclodextrins morphologies to a more porous and amorphous matrix in all lyophilized complexes. XRD patterns indicated a noticeable reduction in drug crystallinity, supporting enhanced potential of the drug solubility. TGA analysis demonstrated improved thermal stability in the inclusion complexes compared to the individual drug and cyclodextrins. Pharmacotechnical evaluation revealed that the obtained formulations (by comparison with physical mixtures formulations) possessed favorable bulk and tapped density values, suitable compressibility index, and good flow properties, making all suitable for direct compression into solid dosage forms. : The improved cyclodextrins formulation characteristics, combined with enhanced dissolution profiles of rivaroxaban comparable to commercial Xarelto 10 mg, highlight the potential of both cyclodextrin inclusion and lyophilization technique as synergistic strategies for enhancing the solubility and drug release of rivaroxaban.
利伐沙班是一种口服抗凝剂，其水溶性较差，这对其生物利用度和治疗效果构成了重大挑战。本研究通过与三种环糊精衍生物（如β-环糊精（β-CD）、甲基-β-环糊精（Me-β-CD）和羟丙基-β-环糊精（HP-β-CD））形成不同的包合物来研究利伐沙班溶解度的提高，这些包合物通过冻干制备，以稳定包合物并改善利伐沙班的溶解特性。：使用傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、X射线衍射（XRD）和热重分析（TGA）分析了各化合物和三种冻干包合物的物理化学性质。：FTIR光谱证实了利伐沙班与环糊精之间形成了非共价相互作用，表明成功地包封到环糊精腔内。SEM图像显示，从纯利伐沙班的晶体结构和环糊精形态显著转变为所有冻干包合物中更具多孔性和无定形的基质。XRD图谱表明药物结晶度明显降低，支持了药物溶解度提高的潜力。TGA分析表明，与单独的药物和环糊精相比，包合物的热稳定性有所提高。药物技术评估表明，所获得的制剂（与物理混合物制剂相比）具有良好的堆密度和振实密度值、合适的压缩指数和良好的流动性，使其都适合直接压制成固体剂型。：环糊精制剂特性的改善，再加上与市售拜瑞妥10 mg相当的利伐沙班溶出曲线的增强，突出了环糊精包合和冻干技术作为提高利伐沙班溶解度和药物释放的协同策略的潜力。
