The Quality Of The Compound Simvastatin Niacin Slow-Released Tablet

On the basis of the related literatures and preparation technology, the quality of the compound simvastatin niacin slow-released tablet was systematically studied in this thesis, and combined with the results of the stability research, the clinical quality standards of this compound formulation was drafted.The compound simvastatin niacin slow-released tablet used in this thesis was developed and prepared by my company, the strength of which is 0.5 g niacin and 20mg for each tablet. This compound slow-released formulation was prepared by coating the niacin tablet by suspension containing simvastatin, in which niacin is the slow released composition and simvastatin is quick released composition.This thesis did the systematic quality study on this self-developed compound formulation, including the identificaiton, dissolution/release rate, related substances, content and content uniformity for the two active ingredients respectively, and established the corresponding detection methods for each test.Identification:for niacin, two methods were used to identify, including chemical identification and ultraviolet spectrophotometry, which both can indentify niacin in the self-developed compound formulation without interferences from the excipients. For simvastatin, two methods including ultraviolet spectrophotometry and HPLC were used to identify, and these two methods both can identify simvastatin in this compound formulation without interfering by the excipients.The dissolution testing methods for Simvastatin:HPLC method was established to test Simvastatin concentration in dissoluted solution. Firstly this method was verified methodologically by blank excipients interference test, linear test, stability test, recovery test and accuracy test. The dihydrogen phosphate buffer (pH 7.0) containing 0.5% sodium dodecyl sulfate sodium was choosed as the dissolving medium, the basket was determined to be the dissolving equipment, with speed 100 rpm, and 45 minutes was selected as the sampling time. The testing results under the above condition showed that the simvastatin dissoluted more than 80% in 45 minutes for 3 batches of the samples, and the RSD between each tablet was less than 5% which meant the dissolution uniformity was good.The release testing methods for niacin:ultraviolet spectrophotometry was choosed, firstly this method was verified methodologically by blank excipients interference test, linear test, accuracy test, stability test, recovery test etc.262nm was the detected wavelength, water was determined as the release medium. The release curve of these 3 batches showed that niacin would be released constantly in 24h, which could met the requirement of this formulation, and the RSD between each sampling point of the 6 tested tablets was less than 5% which meant the dissolution uniformity was good.Related substances in Simvastatin layer:HPLC gradient elution method was choosed, firstly the methodology validation of this method was conducted, including excipients interference experiment, applicability test, the stability test of Simvastati solution, accuracy test, LOQ and LOD determination, destructive testing etc. Under the determined HPLC condition, the peaks of impurites could get good separation from the peak of Simvastatin, indicating that this method has good specificity. These 3 batches of self-developed preparations after testing showed that the biggest impurity was less than 1.0%, and the total impurity was less than 3.0% less 1.0%, which met the requirement in 2010 editon China pharmacopoeia.Related substances in niacin layer:TLC and HPLC method were adopted, firstly the methodology validation of the HPLC method was conducted, including excipients interference experiment, the stability test of niacin solution, accuracy test, LOQ and LOD determination, destructive testing etc. The results by HPLC showed that the total impurity in niacin layer was less than 0.05%. The TLC method was referred to the raw material testing method in 2009 editted BP, the LOD test was conducted. The TLC results showed that no impurities were detected in these 3 batches.Content and content uniformity of Simvastatin:HPLC method was choosed, firstly the methodology validation of this method was conducted, including excipients interference experiment, linear test, the stability test of Simvastati solution, recovery test, accuracy test etc. The content and content uniformity were cuaculated by the peak area using external standard method, the results met the requirement in 2010 editted CP.Niacin content:use acid-base titration to detect the niacin content in this compound. The excipients interference testt, accuracy test, recovery test etc were conducted to validate this mehod. Results showed that the content of these 3 batches were in the limit (95%-105%) of the labelled amount, which met the specification of niacin in CP.Through the systematic quality study, the quality standard of this compound were finally established.