Preperation Of Tribendimidine Enteric-coated Tablets

Intestinal verminosis infections is caused by verminosis in the human intestinal and people is great troubled with intestinal verminosis infections. The deseases cause weight loss and varying severity of gastrointestinal symptoms such as abdominal pain, vomiting, dyspepsia, and so on. China is one of the serious affact countries in the world, the stituation of preventioning and controlling the deseases remain very grim.Tribendimidine is a new medicine explored by Chinese academicians. Through pre-clinical and clinical research show that has many advantages such as fast-acting, high efficacy, minimal side effects, no teratogenic and mutagenic effects, pregnant women and children can be used, and etc. It can be used as a upgrading product for anthelmintics medicines.This topics studied the tribendimidine enteric-coated tablets scientifically, Established the determination methods and effectively overcome the side effects-stimulation of gastric mucosa caused by tribendimidine,and improve the safety and compliance of the drug for patients with it. The main content of this subject include in vitro method for analysis, formulation and process study, quality and stability study, pharmacology and toxicology and clinical research..1.Construction of analysis methods in vitroEstablished main indicators of the quality evaluation of tribendimidine enteric-coated tablets and determination methods.Through methodological study, we development UV spectrophotometric to determination the tribendimidine’s release rate in0.1mol/L HCl and pH6.8PBS and HPLC to its contents and related substances. Results showed that the UV spectrophotometric method is accurate and reliable and HPLC have high sensitivity and selective, it is suitable for tribendimidine enteric-coated tablets’quality control.2. The study of formulation and progressFirst, we studied and optimized the formulation of the core by single factor experiments and orthogonal design method. By single factors we can initial establish the formulation of the core, the excipient in the core has been selected to gannule’angle of repose and core’friability and dissolution and the disintegrating agent has been selected to the tablet pressing, friability and dissolution. Then we can determine the best formulation of the core by further optimizing the formulation on the basis of the initial established formulation.Secondly, the isolation layer and enteric-coated layer’s formulation and process has been optimization based on the film-forming properties of the materials. We can determine the best formulation of isolation layer by dissolving HPMC,PEG6000and polyethyleneglycolsuitable with the proportion2:2:1to obtain5%percent solids, and the best formulation of coated layer’s formulation by further optimizing the formulation selected to the appearance of coating tablet, and the release rate of tribendimidine in0.1mol/L HCl and pH6.8PBS. Results show that we can easily get the reliable and quality products in accordance with the established formulation and process.This preparation process is easy opreated stability, and has a good reproducibility.3. Study on the quality of productsWe established quality standard of tribendimidine enteric-coated tablets and studied the products on the basis of the study of analysis methods in vitro.By the quality standard we can control the qulity comprehensively of the products from the appearance, identification, release, content and related substances in tribendimidine enteric-coated tablets. Results show that the analysis method is accurate and reliable, the quality standard is comprehensive and meet the requirements of products qulity control. The character and identify of products is meet the standard. The release rate of tribendimidine in0.1mol/L HCl is less than10%at the time of2hours and more than80%in pH6.8PBS at the time of45min,the related substances is less2%, and the content is between90～110%, also meet the standard.4. Stability studyWe studied the stablity of tribendimidine enteric-coated tablets by influence factor research, accelerated testing and long-term testing.Influence factor research results show that the quality specification of tribendimidine enteric-coated tablets has no significant change in high humidity(92.5%RH), high temperature(60℃) and strong light(4500Lx), it suggests that the product is stable to light, heat, high humidity,and it is stable on accelerated testing in the conditions of40℃,75%RH and long-term stability testing in the conditions of40℃,75%RH. So the shelf life of products may be tentatively for24months.5. Pharmacolog,Toxicology study and clinical studyStudy on pharmacology shows that tribendimidine is a broad-spectrum anthelmintic and it is very effective to variety of verminosis. Pharmacology and toxicology study shows that LD50of mice is946mg/kg by oral administration and277mg/kg by intraperitoneal injection, and the LD50of rats is3035mg/kg. The non-toxic doses of tribendimidine to rats and dogs is30～150mg/kg/d×l4d and12mg/kg/d×14d. It has low toxicity, free of teratogenic and mutagenic effect of benzimidazoles except some fetaltoxicity in large dose(250mg/kg). Clinical study shows that it is a fast-acting, high efficacy, minimal side effects, a preferred medicine on clinical treatment of intestinal verminosis infections. As we mentioned, the formulation and process of tribendimidine enteric-coated tablets is reasonable and practicable. It is a stable and better quality controlled product that has the advantage of broad-spectrum, fast-acting, high efficacy, minimal side effects, low toxicity, free of teratogenic and mutagenic effect. It has important value and good prospects in clinical and good for social and economic.