Loh Zhiao C, Elkordy Amal A
Faculty of Applied Sciences, School of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, SR1 3SD, UK.
Curr Drug Deliv. 2015;12(4):425-43. doi: 10.2174/156720181204150729125655.
The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system.
本研究的目的是制备和开发含有甲硝唑的片剂剂型，该剂型具有膨胀和漂浮特性，作为一种胃滞留控释药物递送系统，以提高药物的生物利用度。使用羟丙甲纤维素K15M、黄原胶、共聚维酮、尤特奇®RL PO、普朗尼克®F - 127和/或聚丙烯泡沫粉末作为膨胀剂，以及碳酸氢钠（含或不含柠檬酸）作为产气剂，设计了15种不同的泡腾型漂浮系统配方，各成分比例不同。在这15种配方中，选取了6种具有良好片剂漂浮行为的配方，并加入甲硝唑进行进一步研究。通过片剂理化性质、漂浮行为、膨胀能力和药物溶出度研究对片剂进行评估，药物溶出度研究在37°C下使用0.1M盐酸进行8小时。此外，还对粉末混合物进行了傅里叶变换红外光谱（FT - IR）、差示扫描量热法（DSC）和扫描电子显微镜（SEM）分析。除了含有普朗尼克®F - 127作为其缓释成膜聚合物的F11外，大多数片剂显示出良好的理化性质。其他配方表现出高膨胀能力，能够在体外漂浮至少8小时，并具有药物缓释特性。所得数据表明，含有羟丙甲纤维素（12.5%w/w）、黄原胶（25%w/w）、共聚维酮（12.5%w/w）和碳酸氢钠（31.7%w/w）的F3是一种合适的配方，其漂浮滞后时间短，漂浮行为良好，在体外能以零级动力学持续释药至少8小时。羟丙甲纤维素K15M和黄原胶作为膨胀剂的组合在延缓药物释放方面表现出协同作用，适用于提供最持久的药物释放系统。
