title: Buccal bioadhesive delivery system of 5-fluorouracil: optimization and characterization.
abstract: The objective of this work was to apply the response surface approach in the development of buccal bioadhesive tablets of 5-fluorouracil (5-FU). Experiments were performed according to a 3(2) factorial design to evaluate the effects of two polymers, Gantrez MS-955 (X(1)) and hydroxypropylmethyl cellulose (HPMC) K15M (X(2)) on the bioadhesive force, percentage drug release in 8 h (Rel(8 h)), time taken for 50% drug release (t(50%)), and diffusion coefficient (n). The effect of the two independent variables on the response variables was studied by response surface plots and contour plots generated by the Design Expert software. The compatibility between 5-FU and the tablet excipients was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) studies. Both the polymers were found to have synergistic effect on bioadhesion but the effect of Gantrez was more pronounced. A nonlinear twisted relationship was obtained for Rel(8 h) at the intermediate and high levels of the polymers, which indicated an interaction between them at the corresponding factor levels. Kinetic treatment to the dissolution profiles revealed that the drug release ranged from Fickian to anomalous transport, which was mainly dependent on both the independent variables. The desirability function was used to optimize the response variables, and the observed responses were in agreement with the experimental values.
authors.affiliation: New Drug Delivery Research Laboratory, Pharmacy Department, TIFAC Center of Relevance and Excellence in NDDS, Fatehgunj, The M.S. University of Baroda, Vadodara, Gujarat, India.
authors.forename: Munish Kumar
authors.initials: MK
authors.lastname: Dhiman
authors.forename: Pramod D
authors.initials: PD
authors.lastname: Yedurkar
authors.forename: Krutika K
authors.initials: KK
authors.lastname: Sawant
mesh_terms: D000269:Adhesives; D000278:Administration, Buccal; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004344:Drug Incompatibility; D004357:Drug Synergism; D005079:Excipients / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D065347:Hypromellose Derivatives; D007700:Kinetics; D008298:Maleates / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013997:Time Factors
chemical_list: D000269:Adhesives; D000964:Antimetabolites, Antineoplastic; D005079:Excipients; D008298:Maleates; D011145:Polyvinyls; D013607:Tablets; C058026:polyvinylmethoxyethylene-maleic anhydride copolymer; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D005472:Fluorouracil