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一种刺槐豆胶与聚甲基丙烯酸酯 - 羧甲基纤维素钠共混基质,通过水蚀调节实现零级释放。

A Co-blended Locust Bean Gum and Polymethacrylate-NaCMC Matrix to Achieve Zero-Order Release via Hydro-Erosive Modulation.

作者信息

Ngwuluka Ndidi C, Choonara Yahya E, Kumar Pradeep, du Toit Lisa C, Modi Girish, Pillay Viness

机构信息

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

出版信息

AAPS PharmSciTech. 2015 Dec;16(6):1377-89. doi: 10.1208/s12249-015-0326-9. Epub 2015 May 9.

Abstract

Locust bean gum (LBG) was blended with a cellulose/methacrylate-based interpolyelectrolyte complex (IPEC) to assess the hydro-erosive influence of addition of a polysaccharide on the disposition and drug delivery properties inherent to IPEC matrix. The addition of LBG modulated the drug (levodopa) release characteristics of the IPEC by reducing excessive swelling and preventing bulk erosion. After 8 h in pH 4.5 dissolution medium, gravimetric analysis established that IPEC tablet matrix eroded by 30% of the initial weight due to bulk erosion while LBG-blended IPEC (LBG-b-IPEC) demonstrated surface erosion accounting to 62% of initial weight (596→226.8 mg). Mathematical modeling of the drug release data depicted a transformation from non-Fickian mechanism (IPEC matrices) to zero-order drug release pattern (LBG-b-IPEC matrices) with the linearity of release profile being close to 1 (R (2) = 0.99). Physicochemical characterizations employing Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) explicated that LBG interacted with IPEC by its hydrophilic groups associating with the existing water-holding bodies of IPEC to produce compact matrices. The lattice atomistic modeling elucidated that LBG acted as a linker with the formation of intra- and intermolecular hydrogen bonds generating a highly stabilized polysaccharide-polyelectrolytic structure which influenced the improved properties observed.

摘要

将刺槐豆胶(LBG)与基于纤维素/甲基丙烯酸酯的互聚电解质复合物(IPEC)混合,以评估添加多糖对IPEC基质固有处置和药物递送特性的水蚀影响。LBG的添加通过减少过度溶胀和防止整体侵蚀来调节IPEC的药物(左旋多巴)释放特性。在pH 4.5溶解介质中放置8小时后,重量分析表明,由于整体侵蚀,IPEC片剂基质侵蚀了初始重量的30%,而LBG混合的IPEC(LBG-b-IPEC)显示表面侵蚀占初始重量的62%(596→226.8毫克)。药物释放数据的数学建模描绘了从非菲克机制(IPEC基质)到零级药物释放模式(LBG-b-IPEC基质)的转变,释放曲线的线性接近1(R(2)=0.99)。采用傅里叶变换红外光谱(FTIR)和差示扫描量热法(DSC)的物理化学表征表明,LBG通过其亲水基团与IPEC现有的持水体缔合,与IPEC相互作用,从而产生致密的基质。晶格原子模型表明,LBG作为连接体,形成分子内和分子间氢键,产生高度稳定的多糖-聚电解质结构,这影响了所观察到的改善特性。

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