Wang Li Hong, Shang Lei, Shan Dong Yuan, Che Xin
a School of Pharmaceutical Engineering , Shenyang Pharmaceutical University , Shenyang , PR China.
b College of Basic Medical Sciences , Shenyang Medical College , Shenyang , PR China.
Drug Dev Ind Pharm. 2017 Aug;43(8):1343-1350. doi: 10.1080/03639045.2017.1318898. Epub 2017 Apr 27.
In order to overcome the low compliance due to the frequent bladder perfusion of anti-cancer drugs in the treatment of bladder cancer, a long-term control-release of the anticancer drug in the bladder, the floating intravesical preparation was developed. 5-fluorouracil was used as model drug. The floating preparations were prepared by tableting (mini-tablets) and melting (mini-pellets) method. The proportion of 5-fluorouracil and glyceryl tristearate (GTS) was altered among formulations. Dissolution test, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and scanning electron microscope (SEM) were used to investigate the in vitro properties of the formulations. The in vivo evaluation was carried out in beagle dogs. The control-release property of the preparation was not only related to the content of 5-fluorouracil but also related to the preparing method. The releasing time of the mini-tablets was nearly several days, whereas that of the mini-pellets was almost several weeks. DSC and XRPD showed that GTS had polymorphic conversion in the preparing process, therefore, the stabilization procedure was necessary at the end of preparing. In vivo evaluation showed that the prepared long-term floating preparations could maintain an effective 5-fluorouracil concentration in the bladder for about one month, furthermore, in this period the 5-fluorouracil concentration in blood was always far less than that in urine.
为了克服膀胱癌治疗中抗癌药物频繁膀胱灌注导致的顺应性差的问题，开发了一种能在膀胱中长期控释抗癌药物的膀胱内漂浮制剂。以5-氟尿嘧啶作为模型药物。通过压片（小片）和熔融（小丸）法制备漂浮制剂。在不同制剂中改变5-氟尿嘧啶和三硬脂酸甘油酯（GTS）的比例。采用溶出度试验、差示扫描量热法（DSC）、X射线粉末衍射法（XRPD）和扫描电子显微镜（SEM）研究制剂的体外性质。在比格犬体内进行评价。制剂的控释性能不仅与5-氟尿嘧啶的含量有关，还与制备方法有关。小片的释放时间接近几天，而小丸的释放时间几乎为几周。DSC和XRPD表明GTS在制备过程中发生了多晶型转变，因此在制备结束时需要进行稳定化处理。体内评价表明，所制备的长效漂浮制剂可在膀胱中维持有效的5-氟尿嘧啶浓度约1个月，此外，在此期间血液中的5-氟尿嘧啶浓度始终远低于尿液中的浓度。
