Long-term floating control-released intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer.

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.

Drug development and industrial pharmacy. 2017 Apr 12 [Epub ahead of print]

Li Hong Wang, Shang Lei, Shan Dong Yuan, Xin Che

a School of Pharmaceutical Engineering, Shenyang Pharmaceutical University , Shenyang 110016 , China., b College of Basic Medical Sciences, Shenyang Medical College , Shenyang 110034 , China., c School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016 , China.