title: Long-term floating control-released intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer.
abstract: 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.
authors.affiliation: a School of Pharmaceutical Engineering , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Li Hong
authors.initials: LH
authors.lastname: Wang
authors.affiliation: b College of Basic Medical Sciences , Shenyang Medical College , Shenyang , PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shang
authors.affiliation: a School of Pharmaceutical Engineering , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Dong Yuan
authors.initials: DY
authors.lastname: Shan
authors.affiliation: c School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Che
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013607:Tablets / Q000008:administration & dosage*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D013607:Tablets; D005472:Fluorouracil
keywords: 5-fluorouracil; Control-released; bladder cancer; glyceryl tristearate; intravesical