PREPARATION AND EVALUATION OF METRONIDAZOLE SUSTAINED RELEASE FLOATING TABLETS

摘要

Objective: The objective of the present study is the preparation of metronidazole (MZ) floating tablets that are designed to retain in the stomach for a long time for better eradication of Helicobacter Pylori (H. pylori) , a main cause of peptic ulcer disease. Methods: Synthetic and natural polymers were studied for their floating potential in the presence of sodium bicarbonate, namely: hydroxypropyl methylcellulose (HPMC), carbopol 974P, sodium alginate{low and medium viscosity (LV & MV) grades}, locust gum and guar gum. Hardness, floating ability, release profiles and kinetics as well as DSC / FT-IR were studied. Results: Results of both DSC and FT-IR spectroscopy revealed that there was no interaction between the drug and any of the proposed polymers. Carbopol 974P based tablets showed an unacceptable floating lag time (2 h) and did not maintain good tablet integrity. All other formulas were able to float after few seconds and showed buoyancy for more than 24 h. Meanwhile, sustained profiles of MZ release were obtained. After 6 h the amount of MZ released were: 75.11 %, 61.26 %, 54.56 %, 54.25 % and 43.42 % from sodium alginate-LV, HPMC-K4M, guar gum, locust gum and sodium alginate-MV based tablets, respectively. Kinetically, among the 5 assessed models, the release pattern of MZ from the tablets fitted best to Zero order and Hixson & Crowell Cube-Root models. Conclusion: These stomach targeted dosage forms could maintain the minimum inhibitory concentration for sufficient time to allow for local eradication and thereby achieve better efficiency of therapy with improved patient compliance, reduced costs and minimized side effects caused by immediate release dosage forms. Keywords : Metronidazole, Floating tablets, HPMC-K4M, Alginates, Gums, Drug‐polymer interaction, Release kinetics.