| Abjective:The hawthorn leaves flavonoids dispersible tablets were prepared with hawthorn leaves flavonoids, which had extensive definite therapeutic effect for cardiovascular disease. It can reduce myocardial oxygen consumption and increase coronary blood flow thus facilitating low blood viscosity. The supply of myocardial nutritional blood was also increased, which had a significant effect for heart disease with ischemia and hypoxia myocardial. The hawthorn leaves flavonoids dispersible tablets have a positive role in the prevention and treatment, such as coronary heart disease, angina, cardiac arrhythmia, cerebral arteriosclerosis, cerebral insufficiency, cerebral thrombosis, senile dementia and various sequelae because of injuried brain.The dispersible tablets have many virtues, such as disintergration, quick-dissolve and high bioavailability besides the characters of good-stability, easy-taken and easy-carried which the common tablets have. It can be taken directly, swallowing or dissolving it into the water, and so on.This preparation especially suits for the persons who have difficult to swallow and can enhance patients' compliance because of its good taste. So it has got more and more attention of patients.Methods:The single factor variable method and orthogonal experimental design were applied to optimize the prescription. The composition of prescription influencing the preparation qulity was discussed, such as effective disintegration, adhensive and other excipient. The methods controlling preparation quality were researched, especially for HPLC and dissolution.Results:According to the research results, disperable prescription of hawthorn leaves flavonoids were confirmed and 1000 tablets were produced.Friability, dispersal homogeneity and other indexes were all in accord with quality standard.According the confirmed prescription, three continuous batchs of tables as enlarge test were produced in GMP room. Each batch contained 10,000 tablets.The product yield was over 98%. Conduct the test analysis to these three batchs test, all indexes conformed to the requirement of Chinese Pharmacopoeia. Test results indicated that this prescription and technology was reasonable.Referring to the related standards on hawthorn leaves flavonoids tablets and dispersible tablets in the second part of CP2005, we had formulated the quality standard on content determination as well as dissolution determination.The methodology researchs were also studied.The content was determined by UV and the results showed that absorbancy and samples'concentration had a good linear relationship from 8.128 ug/ml to 48.768ug/ml,r=0.9996.The average content of tablet was 28.36mg and the RSD of reproducibility was 1.77%. The RSD of precision was 1.08%.The stability of the experimental results showed that the absorbance value of sample decreased with time, So the sample should be measured immediately after 15 minutes.The average recovery was 98.21%(RSD=1.70%). The results indicated that tablet additives had not influence for content determination of Hawthorn leaves flavonoids dispersible tablets. According to results of content determine, the content of anhydrous rutin was not less than 25.0 mg per tablet, which was about 80% of the amount of total flavonoids.The content was determined by HPLC and the results showed that peak area and samples'concentration had a good linear relationship from 0.0408 ug/ml to 0.3246ug/ml,r=0.9998.The average content of tablet was 0.183mg and the RSD of reproducibility was 1.61%. The RSD of precision was 1.53%.The stability of the experimental results showed that the sample was stable during 8 hours. The average recovery was 99.29%(RSD=1.060%). The results indicated that tablet additives had no influence for content determination of Hawthorn leaves flavonoids dispersible tablets. According to results of content determination, the content of hyperoside was not less than 0.13 mg per tablet.The dissolution of Hawthorn leaves flavonoids dispersible tablets was determined by UV. The methodology research indicated that absorbancy and samples'concentration had a good linear relationship from 4.05ug/ml to 32.4ug/ml,r=0.9999. The RSD of precision was 0.73%. The stability of the experimental results showed that the absorbance value of sample decreased with time, so the sample should be measured immediately after 15 minutes. The average recovery was 100.50%(RSD=1.67%). The results indicated that tablet additives had no influence for dissolution determination of Hawthorn leaves flavonoids dispersible tablets. Three batches of samples were determined by the dissolution test. The results indicated dissolution of flavonoids was over 98% consistent with the standards of more than 70%.Packing with aluminum-model bubble, all indexes had not obvious changes after acceleration-tested for six months under 40℃±2℃, the relative humidity 75%±5%conditions and long-term sample observation tests for six months under 25℃. The results indicated that the samples were stable using this package.Conclusion:According to CP2005 relevant stipulation to dispersible tablets preparation, taking Hawthorn leaves flavonoids as the model medicine, the prescription and the production technology of Hawthorn leaves flavonoids dispersible tablets were studied. The quality control method was established and methodology research and stability research were investgated. All indexes accorded with standards of Chinese Pharmacopoeia. The successfully developed Hawthorn leaves flavonoids dispersible tablets will provide a quick drug for the treatment and prevention of coronary heart disease, angina pectoris and other diseases.
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