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甲芬那酸的超多孔丙烯酸和羟丙基甲基纤维素水凝胶:通过中心复合设计进行配方、表征和优化

Superporous acrylic acid and HPMC hydrogels of mefenamic acid: Formulation, characterization and optimization by central composite design.

作者信息

Khan Hafeez Ullah, Aziz Samar, Maheen Safirah, Khan Ikramullah, Andleeb Mehwish, Younis Hina, Haider Sajjad, Haider Adnan, Akhtar Muhammad Saeed, Shafqat Syed Salman

机构信息

Department of Pharmaceutics, University of Sargodha, Sargodha, Pakistan.

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.

出版信息

Front Bioeng Biotechnol. 2022 Dec 15;10:1057627. doi: 10.3389/fbioe.2022.1057627. eCollection 2022.

Abstract

The purpose of the study was to devise the superporous hydrogels (SPHs) of mefenamic acid (MA) to acquire the sustained action of the MA in the body. The superporous hydrogels of mefenamic acid were formulated by employing the gas blowing method. The central composite rotatable design (CCRD) was applied to optimize the effect of independent formulation factors like acrylic acid (AC), HPMC and glycerol (GLY) over dependent variables like porosity, viscosity, drug content and swelling ratio of superporous hydrogels in water, phosphate buffer (pH 6.8) and in 0.1N HCl (pH 1.2). A number of characteristics such as void fraction, surface morphology by Scanning electron microscopy (SEM) and drug release study were governed along with physico-chemical analysis by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and appraised statistically by employing the ANOVA. The comparative analgesic activity of optimized superporous hydrogel formulation SPH17 was also analyzed by using tail flick method. The Fourier transform infrared spectroscopy and Differential scanning calorimetry studies approved the physical compatibility between the polymers and the drug. The Scanning electron microscopy study specified micrographic insight about the structure of formed formulations comprising presence of pores, fibers and drug-hole aggregates. The superporous hydrogels were detected to be low dense as they expressed density lower than 0.75 g/cc. The decrease in concentration of the polymers and cross linker contributed towards the increase in the void fraction of the superporous hydrogel formulations. The optimized formulation SPH 17 exhibited a highly sustained release of MA for up to 10 h in the both 0.1 N HCl and phosphate buffer (66.6%) media. The non-fickian release of drug revealed the coupling of the diffusion and polymer relaxation mechanism of the drug release from the formulations. The obtained outcomes suggested that analgesic effect of SPH 17 was significantly ( < 0.05) higher than that of simple suspension of mefenamic acid and total analgesic effect duration for superporous hydrogel was also doubled as compared to the duration of analgesic effect produced by drug suspension. The successfully formulated SPH with HPMC K100M as a gelling agent had sustained the action of the mefenamic acid (MF) by improving its poor solubility and permeability. The introduction of inter-penetrating polymeric network (acrylic acid) using glycerol as a cross linker impart increased residence time to superporous hydrogels which ultimately enhanced the feasibility of using superporous hydrogel as oral sustained release devices particularly for gastric retention.

摘要

本研究的目的是设计甲芬那酸(MA)的超多孔水凝胶(SPHs),以实现MA在体内的持续作用。采用气体发泡法制备了甲芬那酸超多孔水凝胶。应用中心复合旋转设计(CCRD)来优化独立配方因素如丙烯酸(AC)、羟丙甲纤维素(HPMC)和甘油(GLY)对超多孔水凝胶在水、磷酸盐缓冲液(pH 6.8)和0.1N盐酸(pH 1.2)中的孔隙率、粘度、药物含量和溶胀率等因变量的影响。通过扫描电子显微镜(SEM)观察孔隙率、表面形态等一系列特性,并通过傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)进行物理化学分析,同时采用方差分析进行统计学评估。还通过甩尾法分析了优化后的超多孔水凝胶制剂SPH17的比较镇痛活性。傅里叶变换红外光谱和差示扫描量热法研究证实了聚合物与药物之间的物理相容性。扫描电子显微镜研究提供了关于所形成制剂结构的微观图像见解,包括孔隙、纤维和药物 - 孔聚集体的存在。检测到超多孔水凝胶密度较低,因为它们的密度低于0.75 g/cc。聚合物和交联剂浓度的降低导致超多孔水凝胶制剂孔隙率增加。优化后的制剂SPH 17在0.1 N盐酸和磷酸盐缓冲液(66.6%)介质中均表现出MA长达10小时的高度持续释放。药物的非菲克扩散释放揭示了药物从制剂中释放的扩散和聚合物松弛机制的耦合。所得结果表明,SPH 17的镇痛效果显著高于甲芬那酸简单混悬液(P < 0.05),并且超多孔水凝胶的总镇痛作用持续时间也比药物混悬液产生的镇痛作用持续时间增加了一倍。成功制备的以HPMC K100M作为胶凝剂的SPH通过改善甲芬那酸(MF)的低溶解度和渗透性,维持了其作用。使用甘油作为交联剂引入互穿聚合物网络(丙烯酸)增加了超多孔水凝胶的停留时间,最终提高了将超多孔水凝胶用作口服缓释装置特别是用于胃滞留的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc79/9797584/abf84f89dee7/FBIOE_fbioe-2022-1057627_wc_sch1.jpg

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