Lee Juseung, Lee Jong-Ju, Lee Seungyeol, Dinh Linh, Oh Hangyu, Abuzar Sharif Md, Ahn Jun-Hyun, Hwang Sung-Joo
College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
Pharmaceutics. 2023 Mar 10;15(3):907. doi: 10.3390/pharmaceutics15030907.
(1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)-a new anticoagulation drug-has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10 cm/s across Caco-2 colonic cells), thus resulting in a low oral bioavailability of <50%; (2) Methods: To solve the drawbacks of conventional APX products, a novel SD of APX in Soluplus was prepared, characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy techniques and evaluated for its solubility, intestinal permeability and pharmacokinetic performance. (3) Results: The crystallinity of the prepared APX SD was confirmed. The saturation solubility and apparent permeability coefficient increased 5.9 and 2.54 times compared to that of raw APX, respectively. After oral administration to the rats, the bioavailability of APX SD was improved by 2.31-fold compared to that of APX suspension (4) Conclusions: The present study introduced a new APX SD that potentially exhibits better solubility and permeability, thus increasing APX's bioavailability.
(1) 背景：固体分散体（SD）有助于提高难溶性药物的生物利用度。同时，阿哌沙班（APX）——一种新型抗凝药物——水溶性低（0.028 mg/mL）且肠道通透性低（跨Caco-2结肠细胞为0.9×10 cm/s），因此口服生物利用度低，小于50%；(2) 方法：为解决传统APX产品的缺点，制备了阿哌沙班在固体分散体Soluplus中的新型制剂，采用差示扫描量热法（DSC）、粉末X射线衍射（PXRD）和傅里叶变换红外光谱（FTIR）技术对其进行表征，并评估其溶解度、肠道通透性和药代动力学性能。(3) 结果：证实了所制备的阿哌沙班固体分散体的结晶度。饱和溶解度和表观渗透系数分别比原料药阿哌沙班提高了5.9倍和2.54倍。大鼠口服给药后，阿哌沙班固体分散体的生物利用度比阿哌沙班混悬液提高了2.31倍。(4) 结论：本研究介绍了一种新型阿哌沙班固体分散体，其可能具有更好的溶解度和通透性，从而提高了阿哌沙班的生物利用度。
