Salem Heba F, Kharshoum Rasha M, Abou-Taleb Heba A, Farouk Hanan Osman, Zaki Randa Mohammed
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Shehata Hegazi Street, P.O. Box 62514 Beni-Suef, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Nahda University (NUB), P.O. Box 62511 Beni-Suef, Egypt.
Pharmaceutics. 2021 Jan 21;13(2):138. doi: 10.3390/pharmaceutics13020138.
Simvastatin (SIM) is a HMG-CoA reductase inhibitor employed in the management of hyperlipidemia. However, its low bioavailability limits its clinical efficacy. The objective of this study was to overcome the poor bioavailability of SIM via the transdermal application of a SIM-loaded niosomal gel. Niosomes loaded with SIM were fabricated by means of the thin-film hydration method and optimized through a 3-factorial design utilizing Design Expert software. The prepared niosomes were evaluated for entrapment efficiency (EE%), zeta potential, vesicle size, and cumulative percentage of drug release. The optimum niosomal formulation was loaded on the gel and evaluated for physical properties such as color, clarity, and homogeneity. It was also evaluated for spreadability, and the cumulative % drug release. The best niosomal gel formula was appraised for ex vivo permeation as well as pharmacokinetic study. The SIM-loaded niosomes showed EE% between 66.7-91.4%, vesicle size between 191.1-521.6 nm, and zeta potential ranged between -0.81-+35.6 mv. The cumulative percentage of drug released was ranged from 55% to 94% over 12 h. SIM-loaded niosomal gels were clear, homogenous, spreadable, and the pH values were within the range of physiological skin pH. Furthermore, about 73.5% of SIM was released within 24 h, whereas 409.5 µg/cm of SIM passed through the skin over 24 h in the ex vivo permeation study. The pharmacokinetic study revealed higher AUC and Cmax with topical application of SIM-loaded niosomal gel compared to topical SIM gel or oral SIM suspension. The topical application of SIM-loaded niosomal gel ascertained the potential percutaneous delivery of SIM.
辛伐他汀（SIM）是一种用于治疗高脂血症的HMG-CoA还原酶抑制剂。然而，其低生物利用度限制了其临床疗效。本研究的目的是通过经皮应用载有SIM的脂质体凝胶来克服SIM生物利用度差的问题。采用薄膜水化法制备载有SIM的脂质体，并通过使用Design Expert软件的三因素设计进行优化。对制备的脂质体进行包封率（EE%）、ζ电位、囊泡大小和药物释放累积百分比的评估。将最佳脂质体制剂负载在凝胶上，并评估其物理性质，如颜色、澄清度和均匀性。还评估了其铺展性和药物释放累积百分比。对最佳脂质体凝胶配方进行了体外渗透以及药代动力学研究。载有SIM的脂质体的EE%在66.7-91.4%之间，囊泡大小在191.1-521.6 nm之间，ζ电位在-0.81至+35.6 mV之间。在12小时内药物释放累积百分比在55%至94%之间。载有SIM的脂质体凝胶澄清、均匀、可铺展，pH值在生理皮肤pH范围内。此外，在24小时内约73.5%的SIM被释放，而在体外渗透研究中，24小时内有409.5 μg/cm的SIM透过皮肤。药代动力学研究表明，与局部应用SIM凝胶或口服SIM混悬液相比，局部应用载有SIM的脂质体凝胶具有更高的AUC和Cmax。局部应用载有SIM的脂质体凝胶确定了SIM经皮给药的潜力。
