Preparation Of Single And Compound Oral Explosive Tablets Of TCBZ And LMS And Pharmacokinetic Evaluation Of TCBZ In Goats

The harm of parasites to animals is very serious.Parasitic diseases can lead to emaciation and anemia of sick animals.They are numerous and widespread.Especially in the southwest,northwest,north and northeast pastoral areas of China,fascioliasis and gastrointestinal nematode disease are particularly common.Gastrointestinal nematode can cause gastroenteritis,make sick animals emaciation,anemia.It seriously hinders the normal physiological function of livestock,so that they can not grow and develop normally,and a large number of adult cattle and sheep die,which not only brings great losses to farmers,but also affects human health and the development of animal husbandry.Praziquantel albendazole and Triclabendazole are commonly used to treat liver fluke in cattle and sheep.Trichlorobendazole is the most common effective anti-fluke drug in clinical practice.It has obvious killing effect on the adults and larvae of the liver fluke in each stage.This drug has a good effect on the liver fluke that has no effect on the treatment of praziquantel and albendazole and has good drug resistance.Drugs used to treat gastrointestinal nematodes include abamectin,ivermectin and Levamisole.Levamisole is a broad spectrum,high efficiency,low toxicity and safe deworming agent commonly used in animal production.Levamisole has high deworming effect on gastrointestinal nematodes,pulmonary nematodes and larvae,as well as immunomodulatory effect.At present,the common dosage forms of traditional tablets and injections in the domestic pharmaceutical market are difficult to feed and inconvenient to transport and store,which are troubling most veterinary pharmaceutical enterprises.Compared with ordinary tablets,oral collapse tablets used in this study have an immediate reaction when exposed to water,and can disintegrate and dissolve rapidly within 30 seconds after entering the mouth without water.Oral collapse tablets have the advantages of fast absorption,easy to take,less intestinal residue and avoiding the liver first-pass effect.It provides convenience for patients with dysphagia,reduces the local stimulation of gastrointestinal tract,and improves the utilization rate and curative effect of drugs.Through the observation test of disintegrant under microscope,the water absorption experiment of disintegrant,the screening experiment of lubricant,the screening experiment of filler and orthogonal experiment,the optimal prescription dosage was selected as microcrystalline cellulose A₁,cross-linked povidone B₂ and mannitol C₂.Aspartame was used as the flavor corrector,magnesium stearate and micropowder silica gel as the lubricant,cross-linked povidone as the disintegrating agent,mannitol and microcrystalline cellulose as the filler.In this study,the single compound oral disintegrating tablets of triclobendazole and levamisole were prepared by powder direct pressing method.According to the above experiments,it can be concluded that the best prescription of compound triclobendazole oral disintegrating tablets is Trichlorobendazole 0.08g,levamisole 0.05g,mannitol content 0.1g PVPP 0.019 g MCC 0.14g,magnesium stearate 0.0036 g,aspartame 0.0324 g,micropowder silica gel 0.0036 g.The best prescription of triclobendazole oral disintegrating tablets was Trichlorobendazole 0.108 g,mannitol 0.0648 g PVPP 0.0108 g MCC0.1008 g,magnesium stearate 0.003 6 g,aspartame 0.0324 g,micropowder silica gel 0.0036 g.The best prescription of levamisole orally disintegrating tablets was levamisole 0.108 g,mannitol 0.0648g,and the content of PVPP was 0.0108 g,MCC 0.1008 g,magnesium stearate 0.0036 g,aspartame0.0324 g,silica gel 0.0036 g.In this study,the quality of three kinds of oral collapse tablets was studied,and a series of tests were carried out on the disintegration time,properties,hardness and brittle degree of the three kinds of oral collapse tablets.In order to simulate the oral cavity of animals,three kinds of oral collapse tablets were put into 5 m L,10 m L,15 m L and 20 m L water respectively to detect the disintegrating effect.The results showed that the disintegrating time of all three kinds of oral collapse tablets was within 20 s,which was in accordance with the provisions of pharmacopoeia and achieved a good disintegrating effect.The hardness and brittleness of the three kinds of tablets were all within the range of 3.0-4.5 kg and 1%respectively,which all met the requirements of pharmacopoeia.This study establish a trichlorobenzene azole and Levamisole content determination method by high performance liquid chromatography?HPLC?,the flow rate of 1 m L/min,the results show that trichlorophenazole within 0.5-50?g/m L linear regression,the regression equation for y=15.305+85.178x,²=0.9999.The Levamisole was subjected to linear regression within the range of 0.05-10?g/m L.The regression equation was y=26537x+1325.8,²=0.9998.The RSD values of recovery and precision were less than 3%.The above experimental results reveal that the method has strong specificity and high precision,and has reached the standard of content detection.In this study,three kinds of oral benzimidazole tablets prepared with the best prescription were selected for stability test,and the drug contents of trichlorobendazole and levamisole in three kinds of oral benzimidazole tablets were detected in high temperature test?60 C?,high humidity test?RH90%?and bright light test?4500 Lx?,as well as the changes of drug appearance and properties were observed.The results showed that the main drug content of the three kinds of tablets decreased slightly,and the powder dropped from the surface of the tablets in the experiment of strong light.Proof that the drug should be kept sealed and out of the light.Through the accelerated stability test,the properties and drug contents of the three kinds of tablets were all stable within 6 months.There are many studies on the pharmacokinetics of Levamisole in cattle and sheep.In this study,only the pharmacokinetic study of Trichlorobendazole in sheep was carried out..Compound oral Trichlorobendazole tablet and single oral Trichlorobendazole tablet were fed to 3 sheep respectively,and 2 m L of blood was collected at 15 different time points after administration.The blood concentration of Trichlorobendazole was substituted into pharmacokinetic software DAS 3.3.1 for data analysis based on the calculation of non-atrioventricular model.The main pharmacokinetic parameters of Trichlorobendazole in plasma were obtained.t_1/2zof Trichlorobendazole was 14.548h and 29.207 h,AUC_?0-t?was 298 h/L*h and 357.15 h/L*h,AUC_?0-??was 305.27 h/L*h and 384.955h/L*h,MRT_?0-t?was 30.575 h and 29.404 h,MRT_?0-??was 32.474 h and 37.258 h,and T_max was 24h and 24 h,respectively.C_max was 7.236?g/L and 9.365?g/L,respectively.According to the experimental results,Triclosbendazole in monofilament tablet reached the half-life earlier,and the maximum blood concentration was higher than that of triclosbendazole in compound.The combination of drugs allows Triclosbendazole to be more widely distributed and stay in the body longer.