Asif Afzal Haq, Desu Prasanna Kumar, Alavala Rajasekhar Reddy, Rao Gudhanti Siva Naga Koteswara, Sreeharsha Nagaraja, Meravanige Girish
Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram 522502, India.
Pharmaceutics. 2022 Mar 8;14(3):584. doi: 10.3390/pharmaceutics14030584.
The purpose of the present research work was to design, optimize, and evaluate fluvastatin-loaded solid lipid nanoparticles (FLV-SLNPs) using 3 factorial design for enhancing the bioavailability. Fluvastatin has several disadvantages, including the low solubility and substantial first-pass metabolism resulting in a low (30%) bioavailability and a short elimination half-life. FLV-SLNPs were prepared using the nano-emulsion technique. For the optimization of the FLV-SLNPs, a total of nine formulations were prepared by varying two independent factors at three levels, using full factorial design. In this design, lipid (A) and surfactant (B) concentrations were chosen as independent factors, whereas entrapment efficiency (Y1) and in-vitro drug release (Y2) were selected as the dependent variables. Additionally, the prepared SLNPs were characterized for X-ray diffraction, Fourier transform-infrared spectroscopy, and differential scanning calorimetry. These studies revealed that there were no interactions between the drug and the selected excipients and the selected formulation components are compatible with the drug. Pharmacokinetic studies in rats confirmed significant improvement in AUC and MRT of SLNPs in comparison with the pure drug indicating the enhanced bioavailability of SLNPs. This study provides a proof-of-concept for the fact that SLNPs can be effectively developed via experimental factorial design, which requires relatively minimal experimentation.
本研究工作的目的是采用三因素设计来设计、优化和评估载有氟伐他汀的固体脂质纳米粒（FLV-SLNPs），以提高其生物利用度。氟伐他汀有几个缺点，包括溶解度低和大量首过代谢，导致生物利用度低（30%）和消除半衰期短。FLV-SLNPs采用纳米乳液技术制备。为了优化FLV-SLNPs，使用全因子设计，通过在三个水平上改变两个独立因素，共制备了九种制剂。在该设计中，脂质（A）和表面活性剂（B）浓度被选为独立因素，而包封率（Y1）和体外药物释放（Y2）被选为因变量。此外，对制备的SLNPs进行了X射线衍射、傅里叶变换红外光谱和差示扫描量热法表征。这些研究表明，药物与所选辅料之间没有相互作用，所选制剂成分与药物相容。大鼠体内药代动力学研究证实，与纯药物相比，SLNPs的AUC和MRT有显著改善，表明SLNPs的生物利用度提高。本研究为通过实验因子设计有效开发SLNPs提供了概念验证，该设计所需的实验相对较少。
