Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets

Abstract

In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

Floating Drug Delivery Systems for Eradication of Helicobacter pylori in Treatment of Peptic Ulcer Disease

“…They concluded that this lasting intra-gastric buoyancy of a controlled release dosage form may also provide a suitable manner to deliver drugs that are locally active to the gastric mucosa in the stomach and, hence, achieve a sitespecific therapeutic action (e.g., antibiotic administration for H. pylori eradication in the treatment of peptic ulcer disease (Sriamornsak et al, 2004 Considering the fact that prolongation of the local availability of the antibacterial agents show positive effects of increasing in the effectiveness of H. pylori treatment ensuring a high drug concentration in the gastric mucosa, we had tried to formulate metronidazole in floating pharmaceutical dosage forms to encounter higher concentrations of the antibacterial agent in the gastric mucosa and clarify the mechanism of the release obtaining a general kinetic model for drug release profiles. In our previously published papers, we had reported the use of two different mechanisms in preparation of metronidazole floating matrix tablets including: A low density producing agent (gas generating agent/porous agent) and hydrocolloid-forming polymer(s) (Asnaashari et al, 2011). Carbonate acted as the gas generating agent when it came into contact with an acidic environment of the stomach under fed condition which got entrapped inside the system, producing bubbles, decreasing the density of the formulation.…”

Design and in Vitro Characterization of Floating Tablets of Metronidazole

“…Peptic ulcers are sores that develop in the lining of the stomach (gastric ulcers), lower esophagus (esophageal ulcers), and/or first part of the small intestine (duodenal ulcers), as a result of inflammation caused by the bacteria H. pylori, erosions, and stomach acids. American College of Gastroenterology guidelines, 2017 for the treatment of H. pylori infection includes the following therapeutic strategies for the first-line treatment, bismuth, proton-pump inhibitors, tetracyclines, and a nitroimidazole (strong recommendation), particularly in those with previous macrolide exposure or are penicillin allergic [4]. Nitroimidazole (metronidazole) antibiotics are most active antibiotics for the treatment and prevention of infections caused by anaerobic bacteria.…”

Formulation development of gastroretentive tablets of lamivudine using the floating-bioadhesive potential of optimized polymer blends

“…carbomers) and non‐ionic (e.g. celluloses) polymers, in this regard, has extensively been employed to attain sustained release and/or gastroretention [8–15] . Accordingly, it is a challenging task to attain the desired floating‐bioadhesive potential and sustained release characteristics of the DDS using a blend of these diversely behaving polymers.…”

“…celluloses) polymers, in this regard, has extensively been employed to attain sustained release and/or gastroretention. [8][9][10][11][12][13][14][15] Accordingly, it is a challenging task to attain the desired floating-bioadhesive potential and sustained release characteristics of the DDS using a blend of these diversely behaving polymers. Systematic studies using Design of Experiments (DoE) could efficiently surmount this hiccup of balancing floatation and bioadhesion employing optimized polymer blends.…”