A comparative study of floating drug delivery system of metronidazole formulated using effervescent and non effervescent techniques

Abstract

This study was carried out to compare effervescent and non-effervescent gastro-floating matrix tablets (GFMT) of metronidazole formulated using Azadirachta indica (Neem) gum (AIG). Neem gum was extracted by a method previously described. Granules were prepared by wet granulation technique using the extracted neem gum at varying concentrations (2, 4, 6 and 8% w/w). Sodium bicarbonate and tartaric acid were used as the gas generating agents for the GFMTs, while ammonium bicarbonate was used as the sublimating agent for the non-effervescent GFMTs. Formulations were either prepared alone with the natural gum or with the addition of 1.0% w/w of acrylate methacrylate copolymer (Eudragit® RL100). All granules were evaluated for micromeritic properties. The granules were compressed at an optimized compression pressure of 30 arbitrary unit on the tableting machine load scale and the non-effervescent GFMTs were sintered at 70 °C for 12 h in a hot-air oven. Tablets were evaluated for hardness, friability, floating lag time, in vitro buoyancy and drug release profiles. Drug-excipient compatibility study was done using Fourier Transform Infra-red Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). Scanning Electron Microscope (SEM) was used to analyze the pores and morphology of the tablets. Results revealed that all formulated floating matrix granules were free flowing, with angle of repose and Carr’s index ≤ 33.2º and ≤ 15.5% respectively. All floating matrix granules were compressible with tablet hardness ≤ 9.0 Kg/cm² . Generally, the percentage friability of the GFMTs decreased with increase in binder concentration (≤ 0.99%). The floating lag time for the effervescent GFMT tablets ranged from 2-7 min, while the non-effervescent formulations had zero floating lag time. FTIR and DSC studies showed that the excipients and the active pharmaceutical ingredient (API) i.e. metronidazole were compatible. SEM reveals the presence of pores and a smooth surface of the non-effervescent GFMTs, while smooth surface with no pores was revealed in the effervescent formulations. Gastro-floating matrix tablets of metronidazole were successfully formulated in this study using the effervescent and non-effervescent techniques and there was significant difference in the floating lag times (P <0.05) while there was no significant difference in the in vitro buoyancy studies in the tablets formulated using both the effervescent and non-effervescent methods (P >0.05).

Keywords: Floating, matrix tablets, effervescent, non-effervescent, buoyancy.