Abstract
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 Cmax at 5 h, and t1/2 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−1 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 LD50 of the enteric sustained-release TTX pellets was 840.13 μg·kg−1, and the ED50 was about 30 μg·kg−1. Thus, the therapeutic index was about 25. The enteric sustained-release TTX pellets with absolute analgesia effect and greatly enhanced safety was prepared.
Highlights
Tetrodotoxin (TTX), found in puffer fish and other terrestrial animals, was identified as a latent neurotoxin
TTX has a significant analgesia effect on cancer pain, acute pain, inflammation pain, neuralgia and the pain caused by arthritis, trauma, burn, and contusion
The mechanism of analgesia may be due to blockage of the voltage-gated sodium channels (VGSCs), leading to decrease of excitatory conduction and nerve impulse of nerve cells at the injury sites, and even influence on plasticity of the nervous system
Summary
Tetrodotoxin (TTX), found in puffer fish and other terrestrial animals, was identified as a latent neurotoxin. The fluid-bed processor can perform multiple tasks like coating, drying, granulation and pelletizing with high efficiency. It protects product against moisture, light and air. Fluid-bed processing embodies advantages like high drug loading and content uniformity. It is specially suitable for the loading of low content drugs [12,13]. In this study, based on the advantages of pellets [14], enteric sustained-release TTX pellets were prepared via fluid-bed processing, to overcome the disadvantages of the TTX injection administrations, like short t1/2 and poor compliance. The acute toxicity study of the pellets was performed in rats
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