Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Udupi, Karnataka, 576 104, India.
AAPS PharmSciTech. 2022 Mar 16;23(4):88. doi: 10.1208/s12249-022-02240-w.
Acquired immunodeficiency syndrome (AIDS) is a condition caused by the infection of a retrovirus namely, human immunodeficiency virus (HIV). Currently, highly active anti-retroviral therapy (HAART), a combination of anti-viral drugs belonging to different classes is considered to be effective in the management of HIV. Ritonavir, a protease inhibitor (PI), is one of the most important components of the HAART regimen. Because of its lower bioavailability and severe side effects, presently, ritonavir is not being used as a PI. However, this drug is being used as a pharmacokinetic boosting agent for other PIs such as lopinavir and in lower doses. The current study aimed to develop nanostructured lipid carriers (NLCs) encapsulating ritonavir to reduce its side effects and enhance oral bioavailability. Ritonavir-loaded NLCs were developed using a combination of two different solid lipids and liquid lipids. Alpha-tocopherol, a well-known anti-oxidant, was used as an excipient (liquid lipid) in the development of NLCs which were prepared using a simple hot-emulsion and ultrasonication method. Drug-excipient studies were performed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). QbD approach was followed for the screening and optimization of different variables. The developed NLCs were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). Furthermore, NLCs were studied for their in vitro drug release profile, and finally, pharmacokinetic parameters were determined using in vivo pharmacokinetic studies. The optimized NLC size was in the range of 273.9 to 458.7 nm, PDI of 0.314 to 0.480, ZP of -52.2 to - 40.9 mV, and EE in the range of 47.37 to 74.51%. From in vitro drug release, it was found that the release of drug in acidic medium was higher than phosphate buffer pH 6.8. Finally, in vivo pharmacokinetic studies revealed a 7-fold enhancement in the area under the curve (AUC) and more than 10-fold higher C with the optimized formulation in comparison to pure drug suspension. Graphical Abstract.
获得性免疫缺陷综合征 (AIDS) 是由逆转录病毒感染引起的疾病，即人类免疫缺陷病毒 (HIV)。目前，高效抗逆转录病毒疗法 (HAART)，即联合使用不同类别的抗病毒药物，被认为是 HIV 管理的有效方法。利托那韦是一种蛋白酶抑制剂 (PI)，是 HAART 方案中最重要的成分之一。由于其生物利用度较低和严重的副作用，目前利托那韦不再作为 PI 使用。但是，这种药物正在被用作其他 PI（如洛匹那韦）的药代动力学增强剂，并且剂量较低。本研究旨在开发包封利托那韦的纳米结构脂质载体 (NLC)，以降低其副作用并提高口服生物利用度。利托那韦负载的 NLC 是使用两种不同的固体脂质和液体脂质组合开发的。α-生育酚是一种众所周知的抗氧化剂，被用作 NLC 开发中的赋形剂（液体脂质），NLC 是使用简单的热乳液和超声方法制备的。药物-赋形剂研究使用傅里叶变换红外光谱 (FTIR) 和差示扫描量热法 (DSC) 进行。使用质量源于设计 (QbD) 方法对不同变量进行筛选和优化。对所开发的 NLC 进行粒径 (PS)、多分散指数 (PDI)、Zeta 电位 (ZP) 和包封效率 (EE) 的表征。此外，还研究了 NLC 的体外药物释放曲线，最后通过体内药代动力学研究确定了药代动力学参数。优化的 NLC 粒径范围为 273.9 至 458.7nm，PDI 为 0.314 至 0.480，ZP 为-52.2 至-40.9mV，EE 为 47.37 至 74.51%。从体外药物释放结果来看，药物在酸性介质中的释放高于磷酸盐缓冲液 pH6.8。最后，体内药代动力学研究表明，与纯药物混悬剂相比，优化配方的 AUC 增加了 7 倍，C 增加了 10 倍以上。
