呋塞米(FSM)的液体自纳米乳化药物递送系统(SNEDDS)已被探索为增强溶解度和渗透性的潜在解决方案,但与快速乳化有关。自发药物释放,体内相关性差。为了克服这个缺点,本研究旨在开发FSM的液体和固体自乳化给药系统,比较配方动力学,继续体内治疗效果,并探讨了固化的优势。为此,使用油酸作为油形成液体SNEDDS(L-SEDDS-FSM),chremophoreEL,吐温80,吐温20作为表面活性剂,和PEG400作为助表面活性剂,含有53mg/mLFSM。同时,固体SNEDDS(S-SEDDS-FSM)通过将液体SNEDDS以1:1的比例吸附到微晶纤维素上来开发。两种配方都进行了尺寸评估,zeta电位,脂肪酶降解,和药物释放。此外,在小鼠中进行了关于尿量的体内利尿剂研究,以研究液体和固体SNEDDS制剂的治疗反应.稀释后,L-SEDDS-FSM显示平均液滴尺寸为115±4.5nm,而S-SEDDS-FSM描绘了116±2.6nm和-5.4±0.55和-6.22±1.2的ζ电位。与L-SEDDS-FSM相比,S-SEDDS-FSM显示脂肪酶的降解降低了1.8倍。S-SEDDS-FSM表现出持续的药物释放模式,在180分钟内释放63%的药物,与L-SEDDS-FSM相比,在30分钟内表现出90%的自发药物释放。与S-SEDDS-FSM相比,L-SEDDS-FSM的尿量迅速增加(1550±56μL),直到研究的第4小时,尿量逐渐增加(969±29μL),提供持续的尿量,但可预测的治疗反应。SNEDDS的固化有效地解决了与液体SNEDDS中观察到的自发药物释放和沉淀相关的挑战。强调固体SNEDDS在改善呋塞米治疗反应方面的潜在益处。
Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 μL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 μL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.