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.