Sustained release delivery of favipiravir through statistically optimized, chemically cross-linked, pH-sensitive, swellable hydrogel

Arooj Khan, Muhammad Zaman, Muhammad Ahsan Waqar, Asif Mahmood, Talal Shaheer, Rai Muhammad Sarfraz, Kanwal Shahzadi, Azmat Ali Khan, Amer M. Alanazi, Milton Kumar Kundu, Md Rabiul Islam, Athanasios Alexiou, Marios Papadakis
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Abstract

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir.
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通过统计优化、化学交联、pH 值敏感、可膨胀的水凝胶持续释放法非拉韦
在当前的研究工作中,利用游离红光聚合技术开发了负载法非拉韦(一种抗病毒药物)的 pH 值响应型聚合物水凝胶。所有水凝胶配方的组成都是通过 Design Expert 11 版的盒式贝肯设计法确定的。聚乙二醇(PEG)用作聚合物,丙烯酸(AA)用作单体,过硫酸钾(KPS)和亚甲基双丙烯酰胺(MBA)分别用作引发剂和交联剂。对所有网络进行了体外药物释放(%)、溶胶-凝胶成分(%)、溶胀研究(%)、孔隙率(%)、夹持效率百分比和化学相容性评估。研究结果表明,溶胀对 pH 值很敏感,pH 值为 6.8 时溶胀最大(2500%)。最佳凝胶成分为 97.8%。尽管水凝胶具有疏水性,但足够的孔隙率使其能够装载大量的法非拉韦。水凝胶对法比拉韦的最大吸附效率高达 98%。药物释放动力学结果表明,根据 R2 值,所开发的大多数配方都遵循 Korsmeyer Peppas 模型。总之,水凝胶技术被证明是制造抗病毒药物法非拉韦缓释制剂的最佳选择。
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