Determination of the intestinal permeability of oseltamivir phosphate from the antiviral drugs by hplc and capillary electrophoresis methods

It requires too long time (about 20 years) and too much cost (800 million-1.2 billion dolars) for a newly discovered molecule with the proven therapeutic activity to be released in markets as a original drug in a dosage form. For this reason, countries that want to reduce their health expenditures get significant savings by using generic drugs which were proven for their bioequivalence by means of original drugs with expired patent protection. According to the survey of the European Generic Medicines Association (EGA) in 2006, Turkey takes the first place among European countries with the supply of 797 million TL and 51,7 % market share. European Medicines Agency pointed out that class 1 and class 3 drugs (according to the BCS, Biopharmaceutical Classification System) may be introduced to the markets without considering bioequivalence study because of fast dissolving as soon as getting inside the body and creating no bioavailability problems. In order to determine the classes of drugs in the BCS that play an important role in the exemption from bioequivalence, it is primarily necessary for the drugs to determine permeation coefficient from intestinal tissue and then to be classified as high or low permeable drug according to the same guidelines. In related work, "Single Pass Intestinal Perfusion" (SPIP) technique was used for the permeability determination and the test drug (oseltamivir), the referance drug (metoprolol tartrate) and a marker without intestinal transit (phenol red) were implemented to the rats. Therefore, analytical methods are necessary for the accurate, reliable and simultaneous analysis of these three components. The aim of our thesis work is to develop some high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods for the determination of intestinal permeability of an antiviral drug active substance, oseltamivir phosphate and investigate some validation parameters such as accuracy, precision, sensitivity and linearity to ensure the method validity due to the lack of work about the intestinal permeability evaluation of related compound by HPLC and CE. The permeability of oseltamivir phosphate was evaluated according to the Biopharmaceutical Classification System by comparing the results obtained via the developed HPLC and CE methods.