Preparation Of Pramipaxole Hydrochloride Sustained-release Tablet And Quality Research

Parkinson’s disease is one of the most common neurodegenerative diseases,drug therapy is priority and it’s the main treatment method.Pramipexole is a non-ergot dopamine agonist with high relative specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. it is believed to be related to its ability to stimulate dopamine receptors in the striatum to alleviate dyskinesia.Pramipexole Immediate release dosage was launched in 1997,and Pramipexole sustained release dosage was approved by FDA in 2010.Now there is no chinese factory who was authorized to produce Pramipexole sustained release dosage. The research and development of pramipexole hydrochloride sustained-release tablets can meet the clinical needs in China.Pramipexole hydrochloride is a BCS I drug, The original manufacturers use carbomer and HPMC as sustained-release material to control the release of pramipexole, This makes the sustained-release tablet dissolve more quickly in acid medium than in intestinal medium.Pramipexole hydrochloride sustained-release tablets in this paper using hydroxypropyl methyl cellulose and calcium phosphate as the main sustained-release materials,the release behavior is similar to that of the original product in both acid medium and intestinal medium.A single factor method was used to investigate the effect of each material on the release rate of the materials. On this basis, a three factor on three level test was carried out by using BOX-BEHNKEN design method based on DOE(experimental of design), the index(f2) of the similarity factor is used to evaluate the similarity of pramipexole hydrochloride release profile between own product with the original product curve, the paper deduced the best form of pramipexole hydrochloride sustained release tablets and we determined its release profiles in different media.The results showed that the release behavior of the self-made products in various media were similar to that of the original product(F2 greater than 50).The quality of pramipexole hydrochloride sustained release tablets were studied and the release and related substances, content determination method has been studied dissolution method has a good specificity, the RSD of repeatability test results is 0.63%, average recovery rate in recovery test is 99.14% on 20%, 50%, 80%, 100% and 120% level, recovery results meet the requirements, pramipexole dihydrochloride quantitation limit is 1.0ng/ml,detection limit is 2.5ng/ml, the method is durability,the slight change in mobile phase or flow rate of does not affect the results.Pramipexole hydrochloride impurities were analyzed on the examination of related substances. The chromatographic conditions can effectively separate all kinds of known impurities, and it is no interference in the blank. In this paper, the methods of linear, repeatability, recovery and detection limit of the impurities are studied.Assay method has a good specificity, the sample solution is stable,the RSD of repeatability test results is 0.52%, average recovery rate in recovery test is 99.84%, recovery results meet the requirements, pramipexole dihydrochloride quantitation limit is 26ng/ml,detection limit is 13ng/ml, the method is durability. the slight change in mobile phase or flow rate of does not affect the results.