Formulation, characterization, and in vitro evaluation of bioadhesive gels containing 5-Fluorouracil.
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.
Dhiman
Munish
M
New Drug Delivery Research Laboratory, TIFAC Center of Relevance and Excellence in NDDS, Pharmacy Department, Fatehgunj, The MS University of Baroda, Vadodara, Gujarat, India.
Yedurkar
Pramod
P
Sawant
Krutika K
KK
D000269:Adhesives; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004339:Drug Compounding; D005079:Excipients; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D005782:Gels; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008298:Maleates; D008567:Membranes, Artificial; D008747:Methylcellulose / Q000031:analogs & derivatives; D015233:Models, Statistical; D020442:Poloxamer; D011145:Polyvinyls; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents; D013696:Temperature; D014783:Viscosity; D014961:X-Ray Diffraction
D000269:Adhesives; D000964:Antimetabolites, Antineoplastic; D005079:Excipients; D005782:Gels; D008298:Maleates; D008567:Membranes, Artificial; D011145:Polyvinyls; D013501:Surface-Active Agents; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; D020442:Poloxamer; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D005472:Fluorouracil