Department of Pharmaceutics, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia.
AAPS PharmSciTech. 2024 Sep 6;25(7):209. doi: 10.1208/s12249-024-02928-1.
The present study aimed to develop and optimize solidified supersaturated self-nanoemulsifying drug delivery systems (SNEDDS) for the combined administration of antihypertensive, antihyperglycemic, and antihyperlipidemic drugs to enhance their solubility and dissolution during the treatment of metabolic syndrome. Various SNEDDS formulations were prepared and subjected to pharmaceutical assessment. The solubility of candesartan (CC), glibenclamide (GB), and rosuvastatin (RC) in SNEDDS and supersaturated SNEDDS formulations was evaluated. The optimized formulation was solidified using Syloid adsorbent at different ratios. Pharmaceutical characterization of the formulations included particle size, zeta potential, in-vitro dissolution, PXRD, FTIR, and SEM analysis. The prepared optimized formulation (F) was able to form homogeneous nanoemulsion droplets without phase separation, which is composed of Tween 20: PEG-400: Capmul MCM (4: 3: 3). It was mixed with 5% PVP-K30 to prepare a supersaturated liquid SNEDDS formulation (F9). In addition, it was found that the addition of PVP-K30 significantly increased solubility CC and GB from 20.46 ± 0.48 and 6.73 ± 0.05 to 27.67 ± 1.72 and 9.45 ± 0.32 mg/g, respectively. In-vitro dissolution study revealed that liquid and solid SNEDD formulations remarkably improved the dissolution rates of CC, GB, and RC compared to pure drugs. XRPD and FTIR analysis revealed that all drugs present in an amorphous state within prepared solidified supersaturated SNEDDS formulation. SEM images showed that liquid SNEDDS formulation was successfully adsorbed on the surface of Syloid. Overall, optimized F9 and solidified supersaturated SNEDDS formulations showed superior performance in enhancing drug solubility and dissolution rate. The present study revealed that the proposed triple combination therapy of metabolic syndrome holds a promising strategy during the treatment of metabolic syndrome. Further in-vivo studies are required to evaluate the therapeutic efficacy of prepared solidified supersaturated SNEDDS formulation.
本研究旨在开发和优化固体超饱和自微乳化给药系统(SNEDDS),用于联合给药抗高血压、抗高血糖和抗高血脂药物,以提高治疗代谢综合征过程中这些药物的溶解度和溶解速率。制备了各种 SNEDDS 制剂并进行了药物评估。评估了坎地沙坦(CC)、格列本脲(GB)和瑞舒伐他汀(RC)在 SNEDDS 和超饱和 SNEDDS 制剂中的溶解度。使用 Syloid 吸附剂以不同比例对优化的制剂进行固化。制剂的药物特性分析包括粒径、Zeta 电位、体外溶出度、PXRD、FTIR 和 SEM 分析。制备的优化制剂(F)能够形成均匀的纳米乳液液滴,而不会发生相分离,其组成是吐温 20:聚乙二醇 400:Capmul MCM(4:3:3)。它与 5% PVP-K30 混合,制备超饱和液体 SNEDDS 制剂(F9)。此外,研究发现,添加 PVP-K30 显著提高了 CC 和 GB 的溶解度,分别从 20.46 ± 0.48 和 6.73 ± 0.05 增加到 27.67 ± 1.72 和 9.45 ± 0.32 mg/g。体外溶出度研究表明,与纯药物相比,液体和固体 SNEDD 制剂显著提高了 CC、GB 和 RC 的溶出速率。XRPD 和 FTIR 分析表明,所有药物在制备的固化超饱和 SNEDDS 制剂中均以无定形态存在。SEM 图像显示,液体 SNEDDS 制剂成功地吸附在 Syloid 的表面上。总的来说,优化的 F9 和固化超饱和 SNEDDS 制剂在提高药物溶解度和溶出速率方面表现出优异的性能。本研究表明,所提出的代谢综合征三联疗法在治疗代谢综合征方面具有很大的潜力。需要进一步的体内研究来评估制备的固化超饱和 SNEDDS 制剂的治疗效果。