Research And Preparation Of Levetiracetam Sustained-release Tablets

The formulation and preparation of Levetiracetam sustained-release tablets(750 mg),in which Levetiracetam was used as the main component and hydroxypropyl methyl cellulose K15 M was used as the sustained-release skeleton material,were studied by release mechanism and response surface design in this paper.It was established that quality evaluation system of Levetiracetam sustained-release tablets which was verified by methodology.At the same time,the influencing factors of the sustained-release tablets were investigated by using the evaluation system.A release curve test method was established.The basket method was used as the dissolution and release test method,and the rotation speed was 100 revolutions per minute.900 m L of buffers with p H of 1.2,4.5,and 6.0 and water were used as dissolution media.Samples were taken after 0.5,1,2,4,6,8 and 10 hours,and tested after dilution by high performance liquid chromatography.At each time point,fluid was replenished with the corresponding medium.Calculate the concentration of each solution by the external standard method,and then calculate the release degree at each time point.The method was proved be feasible by methodological verification,which including specificity,accuracy,linearity,membrane adsorption,and solution stability tests.In the research of prescription ratio and preparation process,firstly,the types of skeleton materials were established through single-factor investigation.HPMC K15 M was selected as the framework material finally.Secondly,the concentration of the skeleton material was studied,and the release results of the prepared tablets were nonlinearly fitted by the first-order equation,Higuchi method,Korsmeyer equation,and Peppas-Sahlin equation.The results showed that when the concentration of skeleton material is less than 20%,the best fit equation is the Korsmeyer equation;when the concentration of skeleton material is more than 30%,the best fit equation is the Peppas-Sahlin equation.Then,by linearly fitting the changes in the parameters of each equations,it was concluded that the turning point of the release behavior is 23.95% of the concentration of the skeleton material: when the concentration is more than the turning point,it appears as controlled release;when the concentration is less than the turning point,it appears as coupling freed.Finally,after examining other excipients and preparation process parameters,a response surface test was designed using four factors and five levels to determine the optimal prescription: 66% of Levetiracetam(LEV),32% of Hydroxypropyl methylcellulose(HPMC,model K15M),0.7% of polyethylene glycol 6000(PEG6000),1.2% of colloidal silica(CSD)and 0.1% of magnesium stearate(MS).The direct pressure method was used for preparation.In terms of quality evaluation studies,the content and related substances of the sustained-release tablets were established in this study.Both were tested by high performance liquid chromatography.According to the specificities of impurities detection,referring to the detection methods of levetiracetam and extended-release tablets in the European Pharmacopoeia 9.4 and the US Pharmacopoeia 42,three sets of methods of related substances for impurity D,impurity G,and other impurities were established which were studied on Levetiracetam extended-release tablets.After methodological verification,every methods had been proved to be credible and feasible.After the research on the formulation process and the establishment of the quality evaluation system,the influencing factors of levetiracetam sustained-release tablets were investigated.Explore its quality changes under harsh conditions.It provides a reference for the storage and transportation conditions of Levetiracetam extended-release tablets.