Dhiman Munish, Yedurkar Pramod, Sawant Krutika K
New Drug Delivery Research Laboratory, TIFAC Center of Relevance and Excellence in NDDS, Pharmacy Department, Fatehgunj, The MS University of Baroda, Vadodara, Gujarat, India.
Pharm Dev Technol. 2008;13(1):15-25. doi: 10.1080/10837450701702438.
The objective of this study was to prepare and evaluate in vitro the bioadhesive gels of 5-Fluorouracil (FU) for the treatment of oropharyngeal cancer. In preformulation study, the physicochemical interactions between FU and polymers were investigated by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, and differential scanning calorimetry (DSC). According to FTIR, XRD, and DSC studies, the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. The gel formulations containing FU were prepared by using Poloxamer 407, HPMC K 15 M, and Gantrez S-97 (polymethylvinylether-co-maleic anhydride). The formulations contained Poloxamer 407 (16-18% w/w) either alone or in combination with HPMC K 15 M and Gantrez S-97. The bioadhesiveness of the gels was found to increase with increasing proportion of HPMC K 15 M and Gantrez S-97. In vitro release studies indicated that release could be sustained up to 8 hr. The permeability coefficients (Kp) of gel across cellulose membrane and buccal mucosal membrane were 1.06 x 10(-4) cm/s and 3.94 x 10(-5) cm/s, respectively, and differed significantly ( p < 0.05). Increasing temperature increased the drug release by increasing drug diffusion despite increase in viscosity. The pH of the release medium showed a very slight effect on the release of FU. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as non-Fickian diffusion.
本研究的目的是制备5-氟尿嘧啶（FU）生物黏附凝胶并进行体外评价，用于治疗口咽癌。在处方前研究中，通过X射线衍射（XRD）、傅里叶变换红外（FTIR）分光光度法和差示扫描量热法（DSC）研究了FU与聚合物之间的物理化学相互作用。根据FTIR、XRD和DSC研究，药物未显示出与所用聚合物相互作用的任何证据，且呈未改变状态。含FU的凝胶制剂采用泊洛沙姆407、羟丙甲纤维素K 15M和甘膦树脂S-97（聚甲基乙烯基醚-co-马来酸酐）制备。制剂单独含有泊洛沙姆407（16 - 18% w/w）或与羟丙甲纤维素K 15M和甘膦树脂S-97联合使用。发现凝胶的生物黏附性随羟丙甲纤维素K 15M和甘膦树脂S-97比例的增加而增加。体外释放研究表明，释放可持续长达8小时。凝胶透过纤维素膜和口腔黏膜膜的渗透系数（Kp）分别为1.06×10⁻⁴ cm/s和3.94×10⁻⁵ cm/s，差异有统计学意义（p < 0.05）。尽管粘度增加，但温度升高通过增加药物扩散而增加药物释放。释放介质的pH对FU的释放影响非常小。体外溶出数据的数学模型表明与Korsemeyer-Peppas模型拟合最佳，药物释放动力学主要为非菲克扩散。
