Department of Pharmaceutics, Kamla Nehru College of Pharmacy, Butibori, Nagpur, Maharashtra, 441108, India.
Department of Pharmaceutics, Suresh GyanVihar University, Mahal, Jagtpura, Jaipur, Rajasthan, 302025, India.
Drug Deliv Transl Res. 2016 Oct;6(5):610-21. doi: 10.1007/s13346-016-0318-7.
The present investigation is aimed to design a statistically optimized self-microemulsifying drug delivery system (SMEDDS) of eprosartan mesylate (EM). Preliminary screening was carried out to find a suitable combination of various excipients for the formulation. A 3(2) full factorial design was employed to determine the effect of various independent variables on dependent (response) variables. The independent variables studied in the present work were concentration of oil (X 1) and the ratio of S mix (X 2), whereas the dependent variables were emulsification time (s), globule size (nm), polydispersity index (pdi), and zeta potential (mV), and the multiple linear regression analysis (MLRA) was employed to understand the influence of independent variables on dependent variables. Furthermore, a numerical optimization technique using the desirability function was used to develop a new optimized formulation with desired values of dependent variables. The optimized SMEDDS formulation of eprosartan mesylate (EMF-O) by the above method exhibited emulsification time, 118.45 ± 1.64 s; globule size, 196.81 ± 1.29 nm; zeta potential, -9.34 ± 1.2 mV, and polydispersity index, 0.354 ± 0.02. For the in vitro dissolution study, the optimized formulation (EMF-O) and pure drug were separately entrapped in the dialysis bag, and the study indicated higher release of the drug from EMF-O. In vivo pharmacokinetic studies in Wistar rats using PK solver software revealed 2.1-fold increment in oral bioavailability of EM from EMF-O, when compared with plain suspension of pure drug.
本研究旨在设计一种统计学优化的甲磺酸依普罗沙坦自微乳给药系统（SMEDDS）。进行初步筛选以找到适合制剂的各种赋形剂的组合。采用 3(2)完全析因设计来确定各种独立变量对依赖（响应）变量的影响。本工作中研究的独立变量是油的浓度（X1）和 S 混合物的比例（X2），而依赖变量是乳化时间（s）、粒径（nm）、多分散指数（pdi）和zeta 电位（mV），并采用多元线性回归分析（MLRA）来了解独立变量对依赖变量的影响。此外，还使用了具有理想性函数的数值优化技术，以开发具有所需依赖变量值的新优化配方。通过上述方法得到的甲磺酸依普罗沙坦优化 SMEDDS 配方（EMF-O）表现出乳化时间为 118.45±1.64s；粒径为 196.81±1.29nm；zeta 电位为-9.34±1.2mV，多分散指数为 0.354±0.02。对于体外溶出研究，将优化配方（EMF-O）和纯药物分别包封在透析袋中，研究表明从 EMF-O 中释放出更多的药物。使用 PK Solver 软件进行的 Wistar 大鼠体内药代动力学研究表明，与纯药物的普通混悬液相比，从 EMF-O 中口服生物利用度提高了 2.1 倍。
