Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
Int J Nanomedicine. 2019 Jul 18;14:5435-5448. doi: 10.2147/IJN.S203311. eCollection 2019.
Ramipril (RMP) suffers from poor aqueous solubility along with sensitivity to mechanical stress, heat, and moisture. The aim of the current study is to improve RMP solubility and stability by designing solid self-nanoemulsifying drug delivery system (S-SNEDDS) as tablet. The drug was initially incorporated in different liquid formulations (L-SNEDDS) which were evaluated by equilibrium solubility, droplet size, and zeta potential studies. The optimized formulation was solidified into S-SNEDDS powder by the adsorbent Syloid and compressed into a self-nanoemulsifying tablet (T-SNEDDS). The optimized tablet was evaluated by drug content uniformity, hardness, friability, disintegration, and dissolution tests. Furthermore, pure RMP, optimized L-SNEDDS, and T-SNEDDS were enrolled in accelerated and long-term stability studies. Among various liquid formulations, F5 L-SNEDDS [capmul MCM/transcutol/HCO-30 (25/25/50%w/w)] showed relatively high drug solubility, nano-scaled droplet size, and high negative zeta potential value. The optimized SNEDDS solidification with Syloid at ratio (1:1) resulted in a compressible powder with an excellent flowability. The optimized tablet (T-SNEDDS) showed accepted content uniformity, hardness, friability, and disintegration time (<15 minutes). The optimized L-SNEDDS, S-SNEDDS, and T-SNEDDS showed superior enhancement of RMP dissolution compared to the pure drug. Most importantly, T-SNEDDS showed significant (<0.05) improvement of RMP stability compared to the pure drug and L-SNEDDS in both accelerated and long-term stability studies. RMP-loaded T-SNEDDS offers a potential oral dosage form that provides combined improvement of RMP dissolution and chemical stability.
雷米普利（RMP）水溶性差，对机械应力、热和湿度敏感。本研究旨在通过设计固体自乳化药物传递系统（S-SNEDDS）作为片剂来提高 RMP 的溶解度和稳定性。该药物最初被纳入不同的液体制剂（L-SNEDDS）中，并通过平衡溶解度、粒径和zeta 电位研究进行评估。优化的配方通过吸附剂 Syloid 固化为 S-SNEDDS 粉末，并压制成自乳化片剂（T-SNEDDS）。对优化的片剂进行药物含量均匀性、硬度、脆碎度、崩解和溶出度试验进行评价。此外，纯 RMP、优化的 L-SNEDDS 和 T-SNEDDS 均被纳入加速和长期稳定性研究。在各种液体制剂中，F5 L-SNEDDS [capmul MCM/transcutol/HCO-30（25/25/50%w/w）] 显示出相对较高的药物溶解度、纳米级粒径和高负 zeta 电位值。用 Syloid 以 1:1 的比例对 SNEDDS 进行优化固化，得到可压缩的粉末，具有优异的流动性。优化的片剂（T-SNEDDS）显示出可接受的含量均匀性、硬度、脆碎度和崩解时间（<15 分钟）。与纯药物相比，优化的 L-SNEDDS、S-SNEDDS 和 T-SNEDDS 均显著提高了 RMP 的溶出度。最重要的是，与纯药物和 L-SNEDDS 相比，T-SNEDDS 在加速和长期稳定性研究中均显著（<0.05）提高了 RMP 的稳定性。载有 RMP 的 T-SNEDDS 提供了一种潜在的口服剂型，可同时提高 RMP 的溶解和化学稳定性。
