Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., 464-3 Jung-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., 464-3 Jung-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea; School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
J Control Release. 2014 Jul 10;185:62-70. doi: 10.1016/j.jconrel.2014.04.034. Epub 2014 Apr 29.
An injectable liquid crystal-forming system (LCFS) was prepared by using sorbitan monooleate (SMO) as a new liquid crystal-forming material for injections, and its potential use of clinically available sustained-release formulation was evaluated. LCFS was prepared using SMO mixed with phosphatidyl choline and tocopherol acetate, and contained 3.75 mg of leuprolide acetate as a monthly dose in 90 μl in liquid form. The semi-solid mesophase was formed from the liquid LCFS when it contacted water. The mesophase showed typical characteristics of the liquid crystalline phase, which was classified as the hexagonal phase. The safety of the LCFS was studied by an in vitro extraction colony assay and by examining the injection site in rats and white rabbits after an autopsy. Both in vitro release test and in vivo pharmacokinetic and pharmacodynamic studies showed a sustained release of leuprolide. When compared with a commercial depot formulation of leuprolide, the LCFS showed a similar AUClast value and significantly reduced initial burst with sufficient suppression of testosterone after subcutaneous injections in rats and dogs. The LCFS can serve as a new type of sustained-release injection formulation for its safety, ease of preparation, and sustained release properties.
一种可注射液晶形成系统（LCFS）被制备出来，使用山梨糖醇单油酸酯（SMO）作为一种新的注射用液晶形成材料，评估其在临床可用的缓释制剂中的潜在用途。LCFS 是由 SMO 与磷脂酰胆碱和醋酸生育酚混合制成的，在 90μl 的液体形式中含有 3.75mg 的醋酸亮丙瑞林作为每月剂量。半固体中间相在 LCFS 与水接触时从液体 LCFS 中形成。中间相表现出典型的液晶相特征，被归类为六方相。通过体外提取集落测定和对大鼠和家兔死后注射部位的检查，研究了 LCFS 的安全性。体外释放试验以及体内药代动力学和药效学研究均显示出醋酸亮丙瑞林的持续释放。与亮丙瑞林的商业储库制剂相比，LCFS 在大鼠和狗的皮下注射后表现出相似的 AUClast 值，明显降低了初始突释，并且对睾酮有足够的抑制作用。LCFS 可以作为一种新型的缓释注射制剂，具有安全性、易于制备和持续释放的特点。
