Design And Evaluation For Oral Preparations Of Hydroxysafflor Yellow A

Hydroxysafflor yellow A (HSYA), the main active ingredient of the safflower plant(Carthamus tinctorius L.), is clinically used to treat cardiovascular and cerebrovasculardiseases, such as myocardial ischemia, brain ischemia, coronary heart disease and cerebralthrombosis. HSYA is a Class III drug in biopharmaceutics classification system (BCS) withthe properties of low membrane permeability and high water-solubility. Due to its lowbioavailability, the way of intravenous administration has to be adopted clinically.However, intravenous administration has poor compliance for patients, therefore oraldosage form needs to be urgently developed. The main obstacle to develop HSYA oraldosage form is how to improve the bioavailability of HSYA, which is exactly the task ofthis research.Physical and chemical properties of HSYA was widely investigated and detected.Dissociation constant (pKa) and oil/water partition coefficient (logP) were firstlydetermined in this research, the results showed that the values of them were8.85±0.01and-4.25±0.03, respectively. Furthermore, the solution stability and photostability ofHSYA was also studied. Based on the results, the pretreatment method and HPLCanalytical method of plasma samples were established.Rats model was established to evaluate the bioavailability of HSYA in vivo. Absorptionenhancers (sodium caprate, sodium deoxycholate, β-CD) and P-gp inhibitors (PEG400,Poloxamer188) were selected to study their enhancing effect on bioavailability of HSYA.The results showed that sodium caprate and PEG400could significantly enhance the BA ofHSYA, so both of them were selected finally to study further.Furthermore, HSYA-chitosan complex were prepared and the preparation process of thecomplex was optimized, the results showed that the binding rate of HSYA-CS complexwas more than99%. Then HSYA granules were prepared mainly using the complex andsodium caprate. The bioavailability of HSYA granules as well as HSYA granules andPEG400were studied and the results indicated that the bioavailability of HSYA granuleswas improved by4.76folds, however, the bioavailability after administration of HSYA granules and PEG400simultaneously was not improved that significantly. It signified thatHSYA granules could not promote the absorption of HSYA with PEG400synergistically.HSYA-EUDRAGIT E100-Capric acid complex (HECC) was prepared and the result ofdissolution test showed that HSYA and capric acid in complex could be slowly andsynergistically released. The experiment of oil/water partition coefficient was performed,by the result, the solubilization fold was nearly4638. Therefore, the bioavailability ofHECC was inspected, the results showed that the Tmaxwas greatly delayed due to theslowly and synergistically released behavior of HSYA and capric acid, and thebioavailability was increased by4.09folds.