Effect of modification of formulation variables on physical characterization of superporouse hydrogel

Safa Mohammed Nser, Athmar Dhahir, Habeeb Al-Shohani, رصن دمحم افص, . امثا
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Abstract

Superporouse hydrogel (SPH) is widely used and investigated as a gastro retentive drug delivery system to extend drug residence time in the stomach   However, their mechanical strength represents a problem because they need to withstand the peristaltic movement of the stomach. Properties of SPH are widely affected by the materials used for their synthesis. The aim of the research is to study the effect of changing the foaming agent and foam stabilizer amount on physical properties, in particular mechanical strength, and drug release from SPH. Trifluoperazine HCl will be used as model drug in the study. SPH formulations was prepared using fixed amount of acrylamide (AM) and polyvinyl alcohol (PVA) as monomers, polyethylene glycol diacrylate (PEGDA) as cross-linker, TRFP as model drug and variable amount of sodium bicarbonate (NaHCO3) as foaming agent, and tween 20 as foam stabilizer.  Ammonium persulphate (APS) / tetramethyl ethylenediamine (TEMED) system was used as polymerization initiator. The effect of changing foaming agent and foam stabilizer on mechanical strength, buoyancy, porosity, density, drug release, drug content, swelling ratio, and swelling time was investigated. Modifying both factors affected all the physical properties and drug release profile. When tween 20 was increased the mechanical strength, density and floating lag time was increased with a reduction in porosity and drug release. While increasing NaHCO3 reduced mechanical strength, density and floating lag time with increased porosity and faster drug release was observed.   Optimum physical properties were observed in formula 2 which had 230 µl of Tween 20 (v/v) and 50 mg of NaHCO3 in which the mechanical strength was 579±0.4, floating lag time 14 min and 80% of the drug was released within 12 hr.  As a conclusion SPH with improved mechanical strength, physical properties and drug release pattern can be achieved by changing foam stabilizer and foaming agent amount in the formulations.    
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配方变量的改变对超多孔水凝胶物理性质的影响
超多孔水凝胶(Superporouse water gel, SPH)作为一种胃保留性给药系统被广泛应用和研究,以延长药物在胃中的停留时间。然而,由于它们需要承受胃的蠕动运动,它们的机械强度是一个问题。SPH的性质受到合成材料的广泛影响。本研究的目的是研究改变发泡剂和泡沫稳定剂的用量对SPH的物理性能特别是机械强度和药物释放的影响。盐酸三氟拉嗪将作为模型药物。以一定量的丙烯酰胺(AM)和聚乙烯醇(PVA)为单体,聚乙二醇二丙烯酸酯(PEGDA)为交联剂,TRFP为模型药物,可变量的碳酸氢钠(NaHCO3)为发泡剂,吐温20为泡沫稳定剂制备SPH配方。采用过硫酸铵(APS) /四甲基乙二胺(TEMED)体系作为聚合引发剂。考察了不同发泡剂和泡沫稳定剂对机械强度、浮力、孔隙率、密度、药物释放量、药物含量、溶胀比和溶胀时间的影响。改变这两个因素会影响药物的所有物理性质和释放特性。增加吐温20的机械强度,密度和漂浮滞后时间增加,孔隙率和药物释放量减少。NaHCO3的增加降低了机械强度、密度和漂浮滞后时间,孔隙度增加,药物释放速度加快。在配方2中,添加230µl Tween 20 (v/v)和50 mg NaHCO3,机械强度为579±0.4,漂浮滞后时间为14 min,药物在12 h内释放80%。结论通过改变配方中泡沫稳定剂和发泡剂的用量,可以获得机械强度、物理性能和药物释放模式均有改善的SPH。
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