Preparation And Quality Analysis Of Liguzinediol Injection And Sustained Release Tablet

Liguzinediol,2,5-dihydroxymethyl-3,6-dimethylpyrazine,is a derivative by modifying the methyl in para-position of Ligustrazine for hydroxymethyl.Ligustrazine is the known alkaloids compontent.Previous pharmacological studies showed that liguzinediol exerted positive inotropic effect on hearts either from normal or model SD rats via targeting on SERCA2a,which is a novel target located in myocardial cell.Liguzinediol could significantly improve the cardiac contractility and the diastolic function without any arrhythmia risk.Liguzinediol is well soluble and can be exploited to be injection for the treatment of acute heart failure in clinical.Moreover,pharmacokinetic investigation indicated that liguzinediol was metabolized rapidly to be short-lived in vivo.In order to prolong the therapeutic effect,considerable efforts were made for the preparation of sustained release.This thesis can be broken down into two major parts:1.Preparation and quality analysis of liguzinediol injectionAccording to research protocols for the same formulation of other drugs,the prescription of liguzinediol injection was formulated and the preparation process was meanwhile investigated by HPLC.Evaluation methods for quality control of liguzinediol injection were established and confirmed to provide new drug development and large-scale production in future with experimental foundations.During the course of preparation,pyrogen examination is the primary index needing to be controlled for injection and,in practical operation pyrogen is removed by adding in adequate active carbon.However,both pyrogen and drug were absorbed by active carbon.To decrease the drug absorption and fully remove pyrogen,the active carbon level is investigated by comparing the changes of drug content and pyrogen conditions with and without active carbon.The sterilization condition was also evaluated.The liguzinediol injection was prepared by referring to the designed process.As for quality control,characterization,identification,clarity and related substances,pyrogen,visible foreign matter,and content determination were performed in three batches.On the basis of the results,quality standard of liguzinediol injection was established.2.Preparation and quality analysis of liguzinediol sustained release tablet.According to research protocols for the same formulation of other drugs,the prescription of liguzinediol sustained release tablet was formulated and the preparation process was meanwhile investigated by HPLC.Evaluation methods for quality standard of liguzinediol sustained release tablet were established and confirmed to provide new drug development and large-scale production in future with experimental foundations.In the process of preparation of liguzinediol sustained release tablet,hydrophilic matrix tablets were prepared with HPMC serving as chief sustained-release material.After the specification and dosage of HMPC were studied,poorly soluble microcrystalline cellulose was chosen as filler,with magnesium stearate being lubricant,liguzinediol sustained release tablets were well produced by wet granulation.Furthermore,the major factors which may influence dissolution rate were also evaluated,such as release device,rotated speed,and dissolution medium.Eventually,prescription and process were established.With regard to quality standard,weight difference,related substances,content and release rate were determined and quality standard was confirmed according to the 2010 edition pharmacopeia.