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基于新型罗望子胶-海藻酸钠的多颗粒制剂,采用响应面法实现了地夫可特的缓释。

Novel tamarind seed gum-alginate based multi-particulates for sustained release of dalfampridine using response surface methodology.

机构信息

Department of Pharmaceutics, Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati 517502, Andhra Pradesh, India; Department of Pharmaceutics, Sri Krishnadevaraya University College of Pharmaceutical Sciences, S.K.University, Anantapuramu, Andhra Pradesh, India.

出版信息

Int J Biol Macromol. 2020 Feb 1;144:725-741. doi: 10.1016/j.ijbiomac.2019.11.203. Epub 2019 Dec 13.

Abstract

The current study involves development of novel tamarind seed gum - alginate complex microspheres for sustained release of dalfampridine by using Central Composite design in combination with response surface methodology. Polymer ratio (A), agitation speed (B) and concentration of CaCl (C) were selected as independent variables. Dalfampridine loaded microspheres are prepared by ionotropic gelation technique and were evaluated for responses. The software numerical optimization process, surface and contour plots predicted the level of independent variables A, B and C (2.6, 800.412 rpm and 1.1%w/w respectively), for maximum response of drug entrapment efficiency (86.09%), controlled release of drug at 1 h, 6 h, 12 h (29.84%, 67.92%, 86.42%) and optimized particle size (613.212 μm) respectively. Low magnitude of relative error for the optimized formulation confirms the validation of model. Optimized formulation was characterized for compatibility by Fourier Transform infrared spectroscopy and Differential scanning calorimetry. The drug release data was best fitted by first order and Higuchi square root model with non-Fickian diffusion kinetics. Therefore, such an attempt of fabrication of dalfampridine multi-particulates system by using tamarind seed gum and sodium alginate may be useful in a better way, for sustaining the release of drug over 12 h.

摘要

本研究采用中心组合设计结合响应面法,开发了新型罗望子胶-海藻酸钠复合微球,用于持续释放二甲苯丙胺。聚合物比(A)、搅拌速度(B)和 CaCl 浓度(C)被选为独立变量。载有二甲苯丙胺的微球通过离子凝胶技术制备,并对其响应进行评估。软件数值优化过程、表面和轮廓图预测了独立变量 A、B 和 C 的水平(分别为 2.6、800.412 rpm 和 1.1%w/w),以获得药物包封效率(86.09%)、药物 1 小时、6 小时和 12 小时的控释(分别为 29.84%、67.92%和 86.42%)和优化的粒径(613.212 μm)的最大响应。优化配方的相对误差较小,验证了模型的有效性。优化配方通过傅里叶变换红外光谱和差示扫描量热法进行了相容性表征。药物释放数据最适合用一级和 Higuchi 平方根模型拟合,具有非 Fickian 扩散动力学。因此,通过使用罗望子胶和海藻酸钠来制造二甲苯丙胺多颗粒系统的这种尝试,可能会以更好的方式,在 12 小时以上持续释放药物。

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