Bandivadeka Mithun Mohanraor, Pancholi Shyam Sundar, Kaul-Ghanekar Ruchika, Choudhari Amit, Koppikar Soumya
Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune, Maharashtra, India.
Drug Dev Ind Pharm. 2012 Jul;38(7):883-92. doi: 10.3109/03639045.2011.631548. Epub 2011 Nov 16.
The main purpose of this work is to formulate self-microemulsifying drug delivery system (SMEDDS) using smaller molecular oil with Atorvastatin calcium as a model drug. Solubility of the selected drug was accessed in oils and surfactants. Percent transmittance (%T) test study was performed to identify the efficient self-microemulsifying formulations. Those formulations which showed higher value for %T were evaluated for droplet size, polydispersity index, ζ potential, refractive index and cloud point measurement. Effect of drug loading on droplet size, increasing dilution in different media, thermodynamic stability and in vitro dissolution was performed to observe the performance of the selected formulation. Further cytotoxicity and permeation enhancement studies were carried out on Caco2 cell lines. Of all the oils accessed for drug solubility, Capmul MCM showed higher solubility capacity for Atorvastatin calcium. Capmul MCM was better microemulsified using combination of Tween 20 and Labrasol surfactant. Droplet size was as low as 86.93 nm with polydispersity index and ζ potential at 0.195 ± 0.011 and -7.27 ± 3.11 mV respectively. The selected undiluted formulation showed refractive index values ranging from 1.40 to 1.47 indicating the isotropicity of the formulation. The selected formulation was robust to dilution in different media and thermodynamically stable. Dissolution profile was enhanced for the selected drug as compared to marketed formulation with t85% and DE values at 10 min and 80.15 respectively. Also cytotoxicity measurement showed minimum effect with good permeation enhancing capacity. Thus our study demonstrates the use of smaller molecular oil (Capmul MCM) for developing self-microemulsifying drug delivery system for better in vitro and in vivo performance.
这项工作的主要目的是以阿托伐他汀钙为模型药物，使用小分子油来制备自微乳化药物递送系统（SMEDDS）。测定了所选药物在油类和表面活性剂中的溶解度。进行了百分透光率（%T）测试研究，以确定有效的自微乳化制剂。对那些显示出较高%T值的制剂进行了粒径、多分散指数、ζ电位、折射率和浊点测量。研究了药物载量对粒径、在不同介质中稀释度增加、热力学稳定性和体外溶出度的影响，以观察所选制剂的性能。进一步对Caco2细胞系进行了细胞毒性和渗透增强研究。在所有用于药物溶解度测定的油类中，Capmul MCM对阿托伐他汀钙表现出更高的溶解能力。使用吐温20和Labrasol表面活性剂的组合能更好地将Capmul MCM微乳化。粒径低至86.93 nm，多分散指数和ζ电位分别为0.195±0.011和-7.27±3.11 mV。所选未稀释制剂的折射率值在1.40至1.47之间，表明该制剂具有各向同性。所选制剂在不同介质中稀释时具有稳定性且热力学稳定。与市售制剂相比，所选药物的溶出曲线得到了改善，t85%和DE值分别在10分钟时为80.15。细胞毒性测量也显示影响最小且具有良好的渗透增强能力。因此，我们的研究证明了使用小分子油（Capmul MCM）来开发自微乳化药物递送系统，以实现更好的体外和体内性能。
