FORMULATION AND EVALUATION OF STOMACH – SPECIFIC NOVEL GASTRO-RETENTIVE FORMULATIONS OF 5-FLUOROURACIL FOR TARGETING GASTRIC CANCER

Intravenous administration of 5-Fluorouracil (5FU) produces severe systemic, dose-related side effects due to its cytotoxic nature, additionally, 5FU is rapidly absorbed from the stomach after oral administration. Therefore a combined floating-bioadhesive tablet (FBT) of 5FU has been developed in order to reduce the dose and associated side effects in other sites of the body. The tablets were prepared by direct compression technique. Hydroxy propyl methyl cellulose (HPMC) K15M was used as a release retardant polymer while carbopol-971P, guar gum and sodium alginate were used as bioadhesive polymer. The pre-compression characteristics shown fair flow behaviour and core tablet properties were within the Pharmacopoeia limit. All formulation batches reported satisfactory floating lag time in a range of 125 – 500 sec and remained buoyant for more than 6 h. Kinetics of dissolution data demonstrated that formulation batch FB4, FB9 and FB10 follow Korsmeyer-Peppas model, FB11 follows first-order kinetics; and FB1, FB2, FB3, FB5, FB6, FB7, FB8, FB12 and FB13 follows Higuchi Matrix model. Analysis of the data revealed that formulation batch FB4 containing HPMC K15M and sodium alginate in the ratio of 4:1 produced the most favourable formulation to develop sustained-release gastroretentive drug delivery system (GRDDS) with optimum drug release pattern and satisfactory physicochemical characteristics. Hence, the formulation batch FB4 was selected as optimized formulation and was kept for further studies.