Study On Dissolution And Bioequiavailability Of The Dihydropyridine Drugs

Three generations of dihydropyridine calcium antagonists were selected and their in vitro dissolution behavoirs were investigated according to the standards of British Pharmacopoeia 2002 and China Pharmacopoeia 2005. They were nifedipine, nimodipine and amlodipine besylate respectively and all of them were commercial products. Similar factor that was recommened by FDA was used as the approach to analyse the dissolution data.Different dissolution media were employed for each product mentioned above under test in order to select situable media what can distinguish more effectively the quality of the commercial products. It was reported that excessive revolution speed of the paddle is apt to cause eddy flow which can not simulate in vivo situations. So different speeds were used to study the effect caused by it. Finally the appropriate dissolution method of each product has been developed including the proper medium and the proper revolution speed of the paddle according to the statistical data of the similar factors and the tolerances of dissolution have been increased for some products.An analytical method for the determination of pharmacokinetics and bioavailability of amoldipine in human plasma has been developed based on liquid chromatography with mass spectrometry. Eighteen healthy male volunteers took 10 mg besylate amlodipine tablet (the test product or the reference product) in a single oral dose in a randomized cross-over design. The maximal plasma concentration of amlodipine was achieved in 4 6 h, c_max were 6.38±0.38 and 6.23±0.43 ng·mL^-1, AUC_0-t were 222.4±52.8 and 214.8±53.2 ng·h·mL^-1, AUC_0-∞ were 266.0±57.0 and 259.5±57.8 ng·h·mL^-1 respectively. The result calculated by 3P97 figured that pharmacokinetic behavior of amlodipine in human conformed with one-compartment model calculated. c_max, AUCo-t and AUC_0-∞ had passed analysis of variance and two one-side test and...