Negi Lalit Mohan, Jaggi Manu, Talegaonkar Sushama
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Pre-clinical Department, Dabur Research Foundation, Ghaziabad, Uttar Pradesh, India.
Int J Pharm. 2014 Jan 30;461(1-2):403-10. doi: 10.1016/j.ijpharm.2013.12.006. Epub 2013 Dec 15.
The present study investigates the screening of the formulation components as well as evaluates the quality issues of the nanostructured lipid carriers (NLCs) for the anticancer agent, CPT-11. The stepwise screening of the components for the preparation of NLCs requires the selection of liquid lipid or oil, based on the relative solubility of CPT-11 in different oils. Maximum solubility of the CPT-11 was found in capmul MCM-C8 (81±0.5 mg/ml). Hence, it was selected as the liquid lipid for the development of NLCs. Solid lipids gelucire 39/1, glyceryl mono stearate (GSM) and compritol ATO 888 were observed to have good affinity for the drug on systematic screening of different solid lipids. However, gelucire 39/1 and GSM were found to have lower physical compatibility (miscibility) with capmul MCM C-8. Hence, compritol ATO 888 was selected as the solid lipid phase for the preparation of NLCs. Ratio of liquid lipid (oil) to solid lipid was optimized with the intention of maximizing the oil concentration (as oil was found to have higher solubility of drug) as well as producing a lipid mix with sufficient melting point to maintain solid state. The liquid-solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (52.48±1.2 °C). Pluronic F-68 was selected as the main surfactant for the preparation of NLCs because of its good emulsification efficacy for the solid lipid liquid mix. The optimized formulation was also evaluated for the different quality issues. PXRD data revealed that the characteristic peaks of the compritol were present in the NLC samples and there was no appreciable polymorphic change when the formulation was stored for 6 months. Electron microscopic and DLS studies proved the absence of different colloidal species. Thermal analysis by DSC revealed that the lipid particles maintained sufficiently good melting point even after nanosizing. Absence of gelation on multiple syringing and resilience for the stress provided by autoclaving further established the quality of the developed NLCs.
本研究对用于抗癌药物伊立替康（CPT - 11）的纳米结构脂质载体（NLCs）的制剂成分进行了筛选，并评估了其质量问题。基于CPT - 11在不同油中的相对溶解度，对制备NLCs的成分进行逐步筛选时需要选择液态脂质或油。发现CPT - 11在辛酸癸酸甘油三酯（capmul MCM - C8）中的溶解度最高（81±0.5 mg/ml）。因此，它被选为开发NLCs的液态脂质。在对不同固体脂质进行系统筛选时，观察到固体脂质聚乙二醇单硬脂酸甘油酯（gelucire 39/1）、单硬脂酸甘油酯（GSM）和十八醇十六醇共聚物（compritol ATO 888）对药物具有良好的亲和力。然而，发现gelucire 39/1和GSM与capmul MCM C - 8的物理相容性（混溶性）较低。因此，选择compritol ATO 888作为制备NLCs的固体脂质相。为了使油浓度最大化（因为发现油对药物的溶解度更高）并制备具有足够熔点以保持固态的脂质混合物，对液态脂质（油）与固体脂质的比例进行了优化。观察到比例高达30:70的液固脂质混合物具有足够的熔点（52.48±1.2℃）。由于泊洛沙姆F - 68对固体脂质液体混合物具有良好的乳化效果，因此被选为制备NLCs的主要表面活性剂。还对优化后的制剂的不同质量问题进行了评估。粉末X射线衍射（PXRD）数据显示，compritol的特征峰存在于NLC样品中，并且制剂储存6个月时没有明显的多晶型变化。电子显微镜和动态光散射（DLS）研究证明不存在不同的胶体种类。差示扫描量热法（DSC）的热分析表明，即使在纳米化后，脂质颗粒仍保持足够好的熔点。多次注射时无凝胶化现象以及对高压灭菌提供的应力具有弹性，进一步证明了所开发的NLCs的质量。
