Ilyas Muzzamil, Rehman Asim Ur, Tayyab Muhammad, Nawaz Malik Marya, Ahmed Naveed, Fatima Humaira
Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan.
Drug Dev Ind Pharm. 2025 Mar;51(3):219-230. doi: 10.1080/03639045.2025.2460062. Epub 2025 Feb 4.
The fabrication of furosemide (FSM) with enhanced oral bioavailability and encapsulation was achieved using a nanostructured lipid carriers (NLCs) drug delivery system.
The uniform drug distribution is a barrier due to its low dose. The lipid-based delivery system was selected based on its poor solubility and permeability, limiting its poor partitioning and solubility in water-based polymeric delivery systems. The lipophilicity of the FSM makes it favorable to partition with triglyceride-based Compritol 888 ATO and oleic acid with minimized drug expulsion, high drug payload, and sustained release over extended time frames.
The Organic and aqueous phases of the microemulsion were stabilized using Tween 80, a hydrophilic surfactant. Box-Behnken design-based optimization was done using alteration in various formulation variables to obtain nano-formulation with the lowest particle size and polydispersity, maximal zeta potential and entrapment efficiency.
Design-Expert yielded several optimized formulations with the desirability function. Maximum desirability was obtained at a particle size of around 178 nm, a surface charge of -19.6 mV, and an EE of above 85%.The release profile depicted 86.5% of cumulative release after 24 h whereas, pharmacokinetic study revealed an increase in C from 0.48 µg/mL (FSM-Suspension) to 0.77 µg/mL (FSM NLCs) to increase the bioavailability to approx. 241% in FSM NLCs. The half-life escalation demonstrated that the residence time of the nanoparticles prolonged at the physiologic pH.
FSM-NLCs exhibited sustained release over a prolonged period, improved residence time in the body, and their action was prolonged.
使用纳米结构脂质载体（NLCs）药物递送系统实现具有增强口服生物利用度和包封率的速尿（FSM）的制备。
由于其低剂量，药物均匀分布是一个障碍。基于其溶解度和渗透性差，选择了基于脂质的递送系统，这限制了其在水基聚合物递送系统中的分配和溶解性差。FSM的亲脂性使其有利于与基于甘油三酯的Compritol 888 ATO和油酸分配，药物排出最小化，药物载量高，并在延长的时间范围内持续释放。
使用亲水性表面活性剂吐温80稳定微乳液的有机相和水相。基于Box-Behnken设计进行优化，通过改变各种制剂变量来获得具有最低粒径和多分散性、最大zeta电位和包封率的纳米制剂。
Design-Expert产生了几种具有期望函数的优化制剂。在粒径约为178 nm、表面电荷为-19.6 mV和包封率高于85%时获得了最大期望值。释放曲线显示24小时后累积释放率为86.5%，而药代动力学研究表明，C从0.48μg/mL（FSM悬浮液）增加到0.77μg/mL（FSM NLCs），FSM NLCs的生物利用度提高到约241%。半衰期的延长表明纳米颗粒在生理pH下的停留时间延长。
FSM-NLCs在较长时间内表现出持续释放，体内停留时间延长，其作用也得到延长。
