Studies On The Stabilities And Pharmacokinetics Of Desloratadine Fumarate Tablets

Desloratadine is one of the third generation Hi-antihistamines, which is used clinically in treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. On account of the instability and incompatibility of desloratadine to lactose, desloratadine fumarate was developed to achieve improvement of the above properties. Such analytical techniques as high-performance liquid chromatography and ultraviolet spectrophotometry were employed to investigate the stabilities and pharmacokinetics of desloratadine fumarate tablets and desloratadine tablets in dogs.1 The development of analytical methods for desloratdine tablets and desloratadine fumarate tabletsAn ion-pair high-performance liquid chromatography method was established to determine the related substance and the content of the formulations. Separation was achieved on a Hypersil BDS Cig column (150mm X 5.0mm ID, Sum) with methanol-0.033mol/L sodium heptanesulfonate- glacial acetic acid (70:30:4, v/v) as the mobile phase and the detection wavelength was set at 241nm.An ultraviolet spectrophotometry method was established to determine the dissolution of the formulations. The third method in Chinese Pharmacopeia (2000 edition) for the dissolution testing was used, and the absorbance of desloratadineand desloratadine fumarate was detected at 241nm and 282nm, respectively.2 The study on the stabilities of desloratadine tablets and desloratadine fumarate tabletsThe compatibility of desloratadine fumarate and lactose was investigated. The changes of the appearance and degradation products (or content) of the mixtures showed that a-lactose monohydrate exhibited no bad effect on the physicochemical stabilities of desloratadine fumarate.The results of stress testing demonstrated that light and temperature had little effect on desloratadine fumarate tablets, while humidity had slight influence. Both the accelerated testing and the long-term testing demonstrated that desloratadine fumarate tablets were as stable as desloratadine tablets.3 The development of a HPLC method for determination of desloratadine in vivo and the study on the pharmacokinetics of desloratadine fumarate tabletsA high-performance liquid chromatography method was established to determine desloratadine in dog plasma. Desloratadine and the internal standard N-methyl-desloratadine were extracted with toluene-isopropanol (95:5, v/v) after alkalization with sodium hydroxide solution and was separated on a Hypersil CN column (150mm X 5.0mm ID, 5um) with the mobile phase of methanol-acetonitrile-0.01mol/L pH5.5 phosphate buffer (35:35:30, v/v), detecting at 241nm. The linear calibration curve was obtained in the concentration range of 5.0ng/ml~ 800.0ng/ml. The low limit of quantitation was 5.0ng/ml.The method was used to study the pharmacokinetics of desloratadine fumarate tablets and desloratadine tablets in 6 dogs after an oral administration of those two products with a dose equivalent to 10mg desloratdine. No significant difference was found between the two products after the analysis of variance (ANVOA) of themain pharmacokinetic parameters. Based on these statistical results, it was concluded that the two products exhibited comparable pharmacokinetic profiles in dogs.The rationale for the development of desloratadine fumarate was that salification would successfully resolve the problem of incompatibility of desloratadine to lactose. What is more, the formulations of desloratadine fumarate achieved perfect stabilities and pharmacokinetic profiles in vivo, which provided a new way for the treatment of allergic disorders.