Development of Candesartan Loaded Solid Lipid Nanoparticles by Box-Behnken Design

Yelugudhari Ramulu, D. Bhikshapathi
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Abstract

The primary motive behind this the present investigation was to develop and optimize the solid lipid nanoparticles formulation of candesartan to enhance solubility and dissolution rate. The prepared SLNs composed of precirol, poloxamer 188, soy lecithin, tween 80, were fabricated employing hot emulsification/ ultrasonication technique. Box-Behnken design was employed for 17 formulation batches in which 3 factors namely lipid, surfactant, and co-surfactant (precirol, poloxamer 188 and soy lecithin) tween 80 weretested at 3 levels of their concentration, i.e., low, medium and high. The effect of different levels of factors was evaluated for the particle size, entrapment efficiency and % cumulative drug release. Kinetic model fitting for candesartan solid lipid nanoparticles (SLN) formulation was done to interpret the release rate from the SLN. Optimized formulation was subjected for fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and stability studies. The mean particle size, PDI, zeta potential, entrapment efficiency, content uniformity and in-vitro drug release of optimized candesartan-loaded SLNs (CD10) were found to be 135.38 ± 3.41 nm, 0.125 ± 0.04, -18.16 ± 2.89 mV, 86.4 ± 2.35%, 99.78 ± 2.54% and 98.91 ± 0.85% respectively. The release kinetics suggested that drug release followed zero-order and release was anomalous non-fickian diffusion super case II transport. FTIR studies revealed no incompatibility between drug and excipients, SEM images exhibited nanoparticles to be more porous and in a spherical shape. Stability studies indicated good stability of the formulation. The proposed way of SLN preparation could be considered a proper method for producing a candesartan-loaded colloidal carrier system.
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Box-Behnken设计制备坎地沙坦固体脂质纳米颗粒
本研究的主要目的是开发和优化坎地沙坦的固体脂质纳米颗粒配方,以提高其溶解度和溶解速度。采用热乳化-超声法制备了由苯醇、波洛沙姆188、大豆卵磷脂、tween 80组成的单链纳米粒子。采用Box-Behnken设计对17个剂型批次进行试验,在低、中、高3个浓度水平下对80个剂型批次的脂质、表面活性剂和助表面活性剂(普瑞罗尔、波洛沙姆188和大豆卵磷脂)进行检测。考察了不同水平因素对其粒径、包封效率和药物累积释放率的影响。采用动力学模型拟合坎地沙坦固体脂质纳米颗粒(SLN)的释放速率。对优化后的配方进行了傅里叶变换红外光谱(FTIR)、扫描电镜(SEM)和稳定性研究。优化后的坎地沙坦sln (CD10)平均粒径为135.38±3.41 nm, PDI为0.125±0.04,zeta电位为-18.16±2.89 mV,含量均匀度为86.4±2.35%,99.78±2.54%,体外释放度为98.91±0.85%。释放动力学表明,药物的释放服从零级,为异常非粘性扩散转运。FTIR研究显示药物和辅料之间没有不相容性,SEM图像显示纳米颗粒更多孔,呈球形。稳定性研究表明该制剂具有良好的稳定性。所提出的SLN制备方法可以被认为是制备坎地沙坦负载胶体载体体系的合适方法。
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