Development of gastroretentive metronidazole floating raft system for targeting Helicobacter pylori

作者：Abou Youssef Nancy Abdel Hamid; Kassem Abeer Ahmed^*; El Massik Magda Abd Elsamea; Boraie Nabila Ahmed

来源：International Journal of Pharmaceutics, 2015, 486(1-2): 297-305.

DOI：10.1016/j.ijpharm.2015.04.004

• Sodium alginate
• Gellan gum
• Glyceryl mono stearate
• Precirol (R)
• Compritol (R)
• Gelation capacity

The study demonstrates the feasibility of prolonging gastric residence time and release rate of metronidazole (Mz) by preparing floating raft system (FRS) using ion-sensitive in situ gel forming polymers. FRSs contained 3, 4, 5 and 0.5, 0.75, 1% w/v sodium alginate (Alg) and gellan gum (G), respectively, 0.25% w/v sodium citrate and calcium carbonate (C). Lipids: glyceryl mono stearate (GMS), Precirol (R) and Compritol (R) were incorporated into G-based formulations (G1%C-1%). Mz:lipid ratiowas 1:1, except for Mz:GMS, ratios of 1:1.5 and 1:2 were also investigated. Buoyancy, gelation capacity and viscosity parameters were evaluated. Drug release and kinetics for selected formulae were examined. The selected lipid containing formula was subjected to an accelerated stability testing.
Alg(4%)C(2%) FRS exhibited short gelation lag time (3 s), long duration (>24 h), floating lag time 1 min and duration >24 h, and a reliable sustained drug release (MDT 6 h). Gellan gum FRSs achieved successful floating gastroretention, but failed to achieve the required gelation capacity. Incorporation of GMS (Mz: GMS 1:1) enhanced the gelation lag time and duration (6 s and >24 h, respectively), keeping sustained drug release and formulation stability. The improved characteristics of the selected FRS make them excellent candidates for gastric targeting to eradicate Helicobacter pylori.

• 出版日期2015-5-30