| The Parkinson’s disease（PD）is the second most prevalent neurodegenerative disease.Patients with Parkinson’s disease are severely limited in their daily activities which brings a heavy burden to the patient’s family.Currently,levodopa is the most commonly used drug for the treatment of PD,but it has high dose and side effects when used alone.Rasagiline is a kind of anti-Parkinsonian monoamine oxidase B（MAO-B）inhibitor,which not only has strong inhibitory effect and low side effects,but also has neuroprotective effect and long-term synergistic effect.Oral disintegrating tablets can disintegrate quickly in the oral cavity without water delivery,and is therefore very suitable for patients with swallowing difficulties such as PD.The development of levodopa/rasagiline combination orally disintegrating tablet is not available at home and abroad,and it is a new drug of Class 2 of the Chemical Drug Registration Classification.This compound orally disintegrating tablet can effectively improve the patient’s medication compliance,and can also effectively reduce the dosage of levodopa,with fewer adverse reactions,which has obvious clinical advantages and good development prospects.This research mainly includes:pre-prescription and prescription process study of compound rasagiline orally disintegrating tablets,quantitative analysis method and methodological study by high performance liquid chromatography（HPLC）,quality and stability study.The main findings are as follows:（1）The compound rasagiline oral disintegrating tablets were prepared by direct compression method,and the optimal prescription was:levodopa 25%,rasagiline mesylate 0.78%,microcrystalline cellulose 33%,mannitol 25.52%,bipolyvinylpyrrolidone cross 7%,sodium bicarbonate 2.7%,anhydrous citric acid2%,acesulfame 2%,micronized silica 1%,magnesium stearate 1%.（2）The HPLC method was established,and the recoveries of the main drugs were all in the range of 98%～102%with the RSD values less than 2%;the intermediate precision RSD values were less than 2%;levodopa showed good linearity in the range of 20μg/m L～680μg/m L and rasagiline in the range of 0.4μg/m L～13.6μg/m L;the limit of quantification（LOQ）of levodopa was 3.2×10-5mg/m L and the limit of detection（LOD）was 9.5×10-6 mg/m L;the LOQ of rasagiline was 0.00019 mg/m L and the LOD was 5.41×10-5 mg/m L.（3）The quality evaluation of the oral disintegrating tablets of compound rasagiline was conducted.The oral disintegrating tablets had smooth appearance,good taste,no gritty feeling,the variation of tablet weight was within the limit of7.5%,the hardness was not less than 30 N,the fragility was less than 1%,the time limit of disintegration in the oral cavity was less than 30 s,the dissolution rate of the main drug was more than 85%within 15 min,more than 90%within 45 min,the content of the main drug was The content of the main drug is 90%～110%of the labeled amount and the content uniformity value is less than 15,and all the indexes of the three batches of preparations meet the requirements of pharmacopoeia.（4）Stability studies have shown that the product is stable under high temperature,high light,high humidity,acceleration and long-term tests,with no change in appearance,tablet weight,content,disintegration time and no degradation products.The results of the above study are of great significance for the quality control of the oral disintegrating tablets of compound rasagiline,which can provide reference for the development of quality standards of the tablets. |
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