Preparation And Pharmacokinetics In The Beagle Dogs Of PTU Sustained-release Tablets

Sustained-release preparation is a kind of formulation type,that can maintain drug release in a long time and keep the plasma drug concentration in a effective range to achieve long-term effects. It has more advantages than normal preparation in treating diseases. The preparation can preserve drug delivery and its level in blood, and it also can prolong the residence time in human body. Therefore, it can reduce the doses of the prescribed medication and its toxic and side-effect. According to the SFDA statistics, recently, extend-release preparation becomes a hotspot in new drugs research, and more and more product varieties appear on the market or be registered on the SFDA.The objective of this article is to make the PTU into a sustained-release preparation by the swellable hydrophilic polymer, and to establish the method of investigating its in vitro release, and also to determine the pharmacokinetics in beagle dogs and to provide the basis for clinical administration.Part One The development of the PTU sustained-release preparationHPMC is a kind of hydrophilic gel matrix which is widely used in the study of sustained release drug delivery system. In this preparation, HPMC and octadecanol were selected as skeleton materials, and lactose as the diluents, and 85% (contained HPMC) alcohol as adhesives, and magnesium stearate as lubricant. The prescription of sustained release tablet of PTU was screened with orthogonal design, and three influencing factors like HPMC, octadecanol and lactose were chosen to determine the optimal prescription and technique. The test result indicates that HPMC and octadecanol hinder the drug release, and the lactose promotes the tablet`s release, and also the HPMC contains in the adhesive has certain effect in vitro release.Part Two The pharmacokinetics of PTU sustained-release tablets in Beagle dogsSix beagle dogs, with 3 males and 3 females, were separated into two groups at random to be issued for the single and multiple dosing regimen of PTU sustained release tablet. And the blood sample was taken after a random crossing oral administration, which was dealt with by precipitator. The HPLC method was developed to determine the concentration of PTU in plasma. A HPLC column of Kromacil C18 (250×4.6mm, 5um) was used with acetonitrile/water/acetic acid(220/770/10, v/v) mobile phase, and the UV test wavelength is 275nm. Sulfadimidine was used as the internal standard. The pharmacokinetic parameter was calculated by the software of DAS2.1.1, and analyzed by using SPSS13.0. The results showed that significant difference was found among Cmax, Tmax, t1/2 between extend release formulation and normal preparation, while no significant difference was found in AUC0~∞between them, which manifested that the test preparation could significantly retard the release process, and lower the peak plasma concentration, meantime, it could also reduce the administration times. So it can be concluded that PTU sustained release formulation can substitute for the normal preparation in clinical medication.