Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 380054, India.
Department of Pharmacology and toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gujarat 380054, India.
Eur J Pharm Sci. 2018 Jan 1;111:257-269. doi: 10.1016/j.ejps.2017.10.008. Epub 2017 Oct 6.
Erlotinib is a well known FDA approved drug from category of tyrosine kinase inhibitors; used for the treatment of lung cancer. However its use is limited because of its poor water solubility.
The aim of present work was to improve solubility by developing a stable nanocrystal based drug delivery system of ERL with the aid of sodium lauryl sulfate as potential stabilizer and to carry out comparative evaluation of electrospraying and lyophilization as solidification techniques on its solid state properties.
Nanocrystal formulation was developed with antisolvent precipitation method having particle size, polydispersity index and zetapotential of 232.4±4.3nm, 0.162 and -9.82mV respectively. Further comparative evaluation of lyophilization and electrospraying was commenced as potential solidification techniques and solid powder matrix obtained from both the solidification techniques were compared in terms of size after re-dispersion (260±4.8 and 329±5.2nm respectively), particle morphology, surface area (0.984±0.11 and 0.341±0.05m/g respectively), pore volume (0.0014 and 0.0009cc/g respectively), solid state of drug present and % drug release (~100% and ~78% respectively in 600min). In vitro cytotoxicity studies shared that obtained formulation was having reduced IC50 values in comparison to drug. Further intracellular reactive oxygen species production was found to be higher for formulation treated cells when compared to free drug. Overall developed formulation was found to be potential drug delivery system for lung cancer therapy.
厄洛替尼是一种广为人知的美国食品药品监督管理局批准的药物，属于酪氨酸激酶抑制剂类别；用于治疗肺癌。然而，由于其水溶性差，其应用受到限制。
本工作的目的是通过开发基于纳米晶体的 ER 药物递送系统来提高其溶解度，该系统在十二烷基硫酸钠的辅助下作为潜在稳定剂，并对静电喷雾和冷冻干燥作为其固态特性的固化技术进行比较评价。
纳米晶体制剂是通过抗溶剂沉淀法制备的，粒径、多分散指数和 Zeta 电位分别为 232.4±4.3nm、0.162 和-9.82mV。进一步比较了冷冻干燥和静电喷雾作为潜在的固化技术，比较了从这两种固化技术获得的固体粉末基质在重新分散后的粒径（分别为 260±4.8nm 和 329±5.2nm）、颗粒形态、表面积（分别为 0.984±0.11m/g 和 0.341±0.05m/g）、孔体积（分别为 0.0014cc/g 和 0.0009cc/g）、药物的固体状态和药物释放百分比（分别为 600min 时约 100%和约 78%）。体外细胞毒性研究表明，与药物相比，所获得的制剂具有降低的 IC50 值。进一步发现，与游离药物相比，用制剂处理的细胞中产生的细胞内活性氧物质更高。总之，所开发的制剂被认为是治疗肺癌的潜在药物递送系统。
