Analgesia Effect of Enteric Sustained-Release Tetrodotoxin Pellets in the Rat

• Published in: Pharmaceutics Vol. 12; no. 1; p. 32
• Main Authors: Hong, Bihong, He, Jianlin, Sun, Jipeng, Le, Qingqing, Bai, Kaikai, Mou, Yanhua, Zhang, Yiping, Chen, Weizhu, Huang, Wenwen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2020; MDPI
• Subjects: Acids; analgesia; Compliance; Drug dosages; enteric pellets; Nervous system; Pain; Pharmaceuticals; pharmacokinetic study; Regression analysis; Sodium; sustained-release; tetrodotoxin; United States > US; China; Germany; pharmacokinetic study; tetrodotoxin; analgesia; sustained-release; enteric pellets
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12010032

Tetrodotoxin (TTX) was identified as a latent neurotoxin that has a significant analgesia effect. It was rapidly absorbed and excreted in rat after intramuscular (i.m.) injection. To maintain the effect, frequent injections were required. The enteric sustained-release TTX pellets with sucrose pellets as a drug carrier was prepared by fluidized bed spray irrigation, coated in sequence with Eudragit NE30D as a sustained-release layer, hydroxypropyl methylcellulose (HPMC) as a barrier layer and Eudragit L30D-55 as an enteric coating. TTX in the pellets could be sustained released for 12 h in dissolution test. In vivo, TTX pellets reached at 5 h, and was 14.52 ± 2.37 h after intragastrically (i.g.) administration in rat. In acetic acid induced writhing test in rat, the pellets at the dosages of 20, 40, 60 and 80 μg·kg produced analgesic effect at about 1.5 h to 9 h and the strongest effect was at about 3 h to 6 h. Simultaneously, the LD of the enteric sustained-release TTX pellets was 840.13 μg·kg , and the ED50 was about 30 μg·kg . Thus, the therapeutic index was about 25. The enteric sustained-release TTX pellets with absolute analgesia effect and greatly enhanced safety was prepared.