Development and evaluation of novel microemulsion based oral formulations of 5-fluorouracil using non-everted rat intestine sac model

Abstract

Oral formulations of 5-fluorouracil (5-FU) with enhanced bioavailability were developed using microemulsion as a drug carrier system. The formulations were evaluated for drug content, physicochemical characteristics such as globule size, zeta potential, viscosity, stability and permeation characteristics. Ex vivo permeation studies were performed using non-everted rat intestinal sac technique. Results of the ex vivo permeation studies revealed that from aqueous solution only 25.08% drug was permeated, whereas, the optimized microemulsion formulation showed 97.5% drug permeation in 8 h, suggesting, approximately, four times enhancement in the drug permeability. Also a 7-fold increase in the flux of drug was observed from microemulsion formulation when compared with the aqueous solution. Further, in vivo pharmacodynamic studies were carried to check the therapeutic efficacy against benzo(a)pyrene [B(a)P]-induced stomach tumors in albino mice (Balb/C strain). The treatment of mice with 5-FU and microemulsion (5-FU II), after the last dose of B(a)P i.e. during the initiation period, resulted in 25% and 67% reduction in tumor incidence, respectively suggesting significant enhancement in the bioavailability and therapeutic efficacy of 5-FU when it was formulated as a microemulsion. These promising results suggest that microemulsion formulation of 5-FU may be used for the treatment of human cancers after pharmacokinetic and clinical evaluation.

Keywords::

• Microemulsion
• 5-fluorouracil
• solubility
• permeability
• benzo(a)pyrene
• non-everted intestinal sac technique
• anti-cancer
• stability
• bioavailability
• metabolism