Preparation And Quality Control Of Aspirin Eugenol Ester Chewable Tablets

Aspirin eugenol ester（AEE）is a novel pharmaceutical compound possessing analgesic,antipyretic,anti-inflammatory,hypolipidemic,antithrombotic,and other pharmacological activity.In the early stage,the pharmacology and toxicology of AEE have been studied,and the safety and effectiveness of AEE have been proved.Studies have shown that AEE has good drug-forming properties.In the studys,the formulation of AEE chewable tablets were screened and assayed including screening safe and stable prescription,and establishing quality standards,in order to lay a foundation for the later clinical research and provide convenience.1.The traits,solubility,and permeability of AEE were explored in the series of pre-prescription studies and the excipients with good compatibility and no adverse interactions compatible excipients were screened by the compatibility experiments of active pharmaceutical ingredients and excipient.2.Through single factor experiments,the appropriate excipients were selected by assessing difficulty of granulation,particle flowability,tablet formability,tablet weight difference,friability and other indicators,then the basic prescription of AEE chewable tablets was drawn up.According to the results of prescription screening,the ratio of raw and auxiliary materials in the basic prescription was further optimized by the L₁₆（4⁵）orthogonal experimental design method and finally the optimal formulation was confirmed.The stability of AEE chewable tablets were investigated under the high temperature,strong light and high humidity.The results showed that the preparation had good stability,which chewable tablets formulation basic items inspect the qualified.The key technological factors such as the pelletize mesh number,drying time and pressure during the production process were optimized,and the control indexes and parameters in the production process of the chewable tablets were established.3.The relevant quality standards of chewable tablets were established by assessing content determination,related substance detection and dissolution determination of the produced.（1）The content determination of AEE chewable tablets was detected by HPLC.The chromatographic conditions were set up as followed:Hypersil ODS（4.6 mm×150 mm,5μm）column,mobile phase methanol:water 77:23（V/V）,UV detection wavelength 279 nm;column temperature 35℃,flow rate 0.9 mL/min,injection volume 10μL,running time 10min.The results showed that content determination of AEE chewable tablets had a good linear relationship with the peak area in the range of 1.0μg⁸0.0μg（R²=0.9998）,the average recovery was 100.1%,and the RSD was 1.21%（n=9）,which suggested that the HPLC method was specificity,accurate,and fast to detect content determination of AEE chewable tablets.（2）A HPLC method for the determination of related substances in AEE chewable tablets was established.The chromatographic conditions were as followed:Hypersil ODS（4.6 mm×150 mm,5μm）,the mobile phase（water∶acetonitrile∶glacial acetic acid∶tetrahydrofuran=70∶20∶5∶5,V/V/V）and acetonitrile is gradient eluted in a certain proportion,UV detection wavelength 279 nm,the column temperature 35℃,the flow rate 10mL/min,the injection volume 10μL,and running time 25 min.The results showed that the linear range of AEE was 2.5μg¹00.0μg（R²=0.9997）,and the reproducibility and stability were in accordance with the requirements.The method can be used for the determination of related substances in AEE chewable tablets.（3）A method for the determination of dissolution of AEE chewable tablets was established.The determination method is slurry method,in which 1.0%sodium dodecyl sulfate-water is used as dissolution medium,rotating speed is 75 r/min,sampling is filtered,a certain amount of precision is taken for 5 times dilution,and determined by UV-vis spectrophotometry.Detection wavelength 279 nm,recording absorbance,calculate the dissolution.The results showed that the method was simple,accurate and reliable,and could be used to determine the dissolution of AEE chewable tablets.4.Based on the above experimental methods and results,the quality of AEE chewable tablets was studied.Quality studies mainly including property,identification,weight difference,brittleness,content determination,related substance examination,dissolution examination and other factors,which provide a reliable theoretical basis and data support for the quantity control of this product.