Study On In Vitrolin Vivo Correlation Of Nitrendipine Tablets

Nitrendipine （NTD） is a dihydropyridine calcium channel antagonist, which is used in the treatment of senile hypertension. There are many brands of nitrendipine tablets in the market, which make a large distance of quality between the nitrendipine tablets of different manufacturers. The aim of this paper is to improve the quality of drugs of differet brands, make the same effect to every kind of patients by in vitro/in vivo correlation test.Ultraviolet spectrophotometry （UV） method was developed for in vitro assay of the content of nitrendipine tablets. The content of nitrendipine tablets of ten brands were determined. The content uniformity of nitrendipine tablets of ten brands were investigated according to the standard of Chinese Pharmacopoeia 2005.Ultraviolet spectrophotometry （UV） method was applied to determined the equilibrium solubility in various kinds of dissolution mediums. Different methods were chosen to investigate the dissolution behaviors of nitrendipine tablets of ten brands. First, the method of Chinese Pharmacopoeia 2005 and Pharmacy Japan-Orange book were used to evaluate the quality of nitrendipine tablets of ten brands. The concentration of SDS, pH and the rate of rotation were changed to determine the dissolutions. Similar factor that was recommended by FDA was used to analyse the dissolution data to find a strict and rational dissolution method to control the quality of nitrendipine tablets of differet manufacturers.The concentration of nitrendipine in beagle dogs’ plasma was assayed by high-performance liquid chromatography （HPLC）. The plasma concentration was tested after a single oral administration of nitrendipine tablets of three brands. One was the best of them, and the others have a large distinguish in dissolution behaviors. Plasma concentration-time profiles were determined by HPLC. The pharmacokinetics parameters after a single oral administration of nitrendipine tablets analyzed by non-compartment model theory were AUC_0～t 524.28±35.18 ng·h/mL, 217.21±99.20 ng·h/mL and 267.99±127.24 ng·h/mL, c_max220.47±64.47 ng/mL, 57.41±20.68 ng/mL and 136.19±78.19 ng/mL, t_max1.5 h±0 h, 1.8±0.3 h and 1.7±0.6 h, respectively. A parallel correlation was obtained between the absorption in vivo of nitrendipine tablets of three brands and the dissolution using 0.5% SDS solution as dissolution medium.The correlations of in vitro/in vivo of nitrendipine tablets were calculated using Loo-Riegelman method, and the better correlation existed between absorption percent in vivo and the dissolution in vitro in 0.5% SDS solution than the method of Chinese Pharmacopoeia 2005 and in 0.5% SDS solution at the higher rate of rotation.The results of this paper showed that the method: 0.5% SDS solution, 900 ml, paddles, 75 r/min, the dissolution of nitrendipine tablets were no less than 70% at 45 min were chosen as a rational method to control the quality of nitrendipine tablets of different manufactuters.