| Agomelatine tablets Servier is developed by Les Laboratoires Servier in that France the have a significant effect in antidepressant.It's not available in our country currently. It is a conventional film-coated tablets,and the main component is in an amount of 25 mg, and it can treat all kinds of depression virtually. It has better effect compared to conventional drugs, little side effect, so it ‘s widely used in doctors and patients.Although Agomelatine has a good oral absorption, but the bioavailability is low because of the large first pass effect and individual differences, so the treatment of agomelatine has not been fully exploited. Aiming at this great flaw of this medicine, we decided to change the mode of it's administration to solve this problem. Considering using the new mode of administration by sublingual giving to make it into sublingual tablets.so it can maximum avoid to these drawbacks to play to their strengths fully for the benefit of the majority of patients.Objective: To prepare the agomelatine sublingual tablets, and measure the pharmacokinetic parameters of sublingual tablets and common tablets in beagle dogs, and compare two formulations of pharmacokinetic parameters to investigate whether it can achieve the intended purpose.Methods: In this study, the physical and chemical properties of the drug will be studied fully, and a series of prescription has been screened to determine the final formulation and preparation combined with the quality standards of sublingual tablets.Agomelatine tablets and sublingual tablets have been took in beagle dogs after developing the sublingual tablets,and blood at different time,then compare and calculate the pharmacokinetic parameters of them.Results: Before the prescription screening, fully we investigate the properties of agomelatine drug and various materials,such as lactose, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, polyethylene glycol 4000, aspartame, poloxamer materials, on the basis of single factor on the prescription was optimized by orthogonal test. The test results showed that the prescription design that has been optimizated is more appropriate and the preparation process is stable relatively.So the sublingual tablets has good reproducibility in three batches.We Established the detection methods of dissolution and content abourt agomelatine. The results proved that each method is accurate and reliable, specific, precision, and it can effectively control the quality of sublingual tablets. The result shows that the factors such as appearance, tastey,disintegration, dissolution, content and related substances the indexes are all meet the requirements.Due to the time constraints,we are not continue to do post-study experiments and accelerate long-term experiments. The result showed that the sublingual tablets have good stability.The test shows that sublingual tablets have been available for pharmacokinetic studies. It can solve the problem of low bioavailability and individual differences by pharmacokinetic studies.The sublingual tablets have been available for pharmacokinetic test. The result is that sublingual tablets and conventional tablets Tmaxwere(0.22±0.14) h and(0.54±0.36) h;Cmaxwere(59.72±29.11) ng/m L and(90.05±46.02)ng/m L; AUC(0 ~ 6h)were(28.91±10.59) and(79.56±41.48).Conclusion: The result can be seen from this study that the preparation process of antidepressant agomelatine sublingual tablets is maturely.In the based on the pharmacokinetic plasma concentration with beagles, and the result shows that the time to peak of sublingual tablets is earlier than conventional tablets and the drug is rapidly absorbed, but Cmaxand AUC lower than the conventional tablets.Even it is not achieved the desired effect,but the huge significance have been showed for subsequent study. |
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