Sulaiman Bin Abdullah Aba Al-Khail - Centre for Interdisciplinary Research in Basic Science (SA-CIRBS), International Islamic University, Islamabad 44000, Pakistan.
Riphah Institute of Pharmaceutical Sciences (RIPS), Riphah International University, Lahore Campus, Lahore 54770, Pakistan.
Medicina (Kaunas). 2019 May 24;55(5):210. doi: 10.3390/medicina55050210.
Lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions by modest adjustments and offer many valuable opportunities in drug delivery. Chlorpromazine, an antipsychotic agent with poor aqueous solubility-with extensive first-pass metabolism-can be a suitable candidate for the development of SNEDDS. The current study was designed to develop triglyceride-based SNEDDS of chlorpromazine to achieve improved solubility, stability, and oral bioavailability. Fifteen SNEDDS formulations of each short, medium, and long chain, triglycerides were synthesized and characterized to achieve optimized formulation. The optimized formulation was characterized for several in vitro and in vivo parameters. Particle size, zeta potential, and drug loading of the optimized SNEDDS (LCT) were found to be 178 ± 16, -21.4, and 85.5%, respectively. Long chain triglyceride (LCT) showed a 1.5-fold increased elimination half-life (p < 0.01), up to 6-fold increased oral bioavailability, and 1.7-fold decreased plasma clearance rate (p < 0.01) compared to a drug suspension. The findings suggest that SNEDDS based on long-chain triglycerides (LCT) formulations seem to be a promising alternative for improving the oral bioavailability of chlorpromazine.
基于脂质的自微乳给药系统（SNEDDS）通过适度调整重新引起了纳米乳的关注，并在药物传递方面提供了许多有价值的机会。氯丙嗪是一种水溶性差且具有广泛首过代谢的抗精神病药物，可作为 SNEDDS 开发的合适候选药物。本研究旨在开发基于甘油三酯的氯丙嗪 SNEDDS，以实现溶解度、稳定性和口服生物利用度的提高。合成并表征了十五种短链、中链和长链甘油三酯的 SNEDDS 配方，以实现优化的配方。对优化的 SNEDDS（LCT）进行了多种体外和体内参数的表征。优化 SNEDDS 的粒径、Zeta 电位和载药量分别为 178±16nm、-21.4mV 和 85.5%。与药物混悬剂相比，长链甘油三酯（LCT）显示出 1.5 倍的消除半衰期延长（p<0.01），高达 6 倍的口服生物利用度提高，以及 1.7 倍的血浆清除率降低（p<0.01）。这些发现表明，基于长链甘油三酯（LCT）的 SNEDDS 配方似乎是提高氯丙嗪口服生物利用度的有前途的替代方案。
