Baheti Ankit, Srivastava Saurabh, Sahoo Deepak, Lowalekar Rohit, Panda Bibhu Prasad, Padhi Bijay Kumar, Raghuvanshi Rajeev
Proprietary Products, Formulation R&D Block 'C', IPDO Innovation Plaza Survey Nos. 42,45,46 &54 Bachupally, Qutubullapur R.R. Dist. -500072, A.P. (India).
Curr Drug Deliv. 2015 Jan 20.
Objective: The aim of this study was to develop a formulation for lymphatic uptake with enhanced solubility of antifungal drug, terbinafine by use of self-microemulsifying drug delivery system (SMEDDS); suitable enough to be an industrially feasible and acceptable dosage form. Methods: Fabrication of pseudo ternary phase diagram was done with suitable oils, surfactants and co-surfactants. The optimized formulation was characterised for droplet size, polydispersity index, zeta potential, cross-polarized light microscopy, thermodynamic stability, viscosity, capsule compatibility and evaluated for in vitro- in vivo parameters. The formulation was tested in animal model for lymphatic uptake with and without chylomicron blocking agent followed by the pharmacokinetic evaluation of the same. Results: The self-emulsification time, droplet size, polydispersity index of the optimized formulation remained unaffected in different media (water, 0.1N HCl and phosphate buffer pH 6.8) over stability conditions and with time. Crossed-polarized light microscopy examination of diluted SMEDDS formulation indicated that the dispersion was an isotropically stable system. The rate of dissolution for SMEDDS formulation was almost double as compared to marketed formulation (Lamisil®). Current investigation indicated a potential for lymphatic uptake of lipid based SMEDDS formulation with enhanced solubility of the candidate drug terbinafine. The optimum formulation of terbinafine SMEDDS when orally administered to rat with and without chylomicron flow blocking agent (cycloheximide) showed the area under the curve (AUC0-48hrs) as 10168.17 ng h/ml and 7425.44 ng h/ml respectively indicating the absorption through the lymphatic route. Thus, the study shows use of SMEDDS formulation for the drug delivery by lymphatic uptake.
本研究的目的是通过使用自微乳化药物递送系统（SMEDDS）开发一种用于淋巴管摄取的制剂，以提高抗真菌药物特比萘芬的溶解度；该制剂要足够适合成为一种工业上可行且可接受的剂型。方法：用合适的油、表面活性剂和助表面活性剂制作伪三元相图。对优化后的制剂进行液滴大小、多分散指数、zeta电位、交叉偏振光显微镜检查、热力学稳定性、粘度、胶囊相容性等特性表征，并评估其体外-体内参数。在动物模型中测试该制剂在有和没有乳糜微粒阻断剂的情况下的淋巴管摄取情况，随后对其进行药代动力学评估。结果：在不同介质（水、0.1N盐酸和pH 6.8的磷酸盐缓冲液）中，在稳定性条件下以及随时间变化，优化后制剂的自乳化时间、液滴大小、多分散指数均未受影响。对稀释后的SMEDDS制剂进行交叉偏振光显微镜检查表明，该分散体是各向同性稳定体系。SMEDDS制剂的溶出速率几乎是市售制剂（兰美抒®）的两倍。当前研究表明，基于脂质的SMEDDS制剂有淋巴管摄取的潜力，可提高候选药物特比萘芬的溶解度。当给大鼠口服含和不含乳糜微粒流动阻断剂（环己酰亚胺）的特比萘芬SMEDDS最佳制剂时，曲线下面积（AUC0 - 48hrs）分别为10168.17 ng h/ml和7425.44 ng h/ml，表明通过淋巴途径吸收。因此，该研究表明可使用SMEDDS制剂通过淋巴管摄取进行药物递送。
