Studies On The Sustained-Release Pellets Of Dipyridamole

Dipyridamole(persantine)plays aimportant role in antithrombokinesis and expanding vascellum.It could inhibit platelet aggregation and is used to prevent and cure angina,prevent recurring myocardial infarction and thromb in clinic and so on.The biological half-life of Dipyridamole is short,and patients need take medicine three or four times every days.The sustained-release pellets were prepared in this text,in order to reduce administration frequency,to lower concentration in plasma and side effect,thus to improve compliance.UV method was established to assay contents and release percent of Dipyridamole.Equilibrium solubility of Dipyridamole in different pH media was determined.Sustained-release beads were prepared using MCC,carbopol 974P, Xanthan gum,octadecanol,glyceryl monostearate employing extrusion-spheronization method.Quality of these beads were evaluated.Mixtured sustained-release beads of matrix with sustained release pellets of membrane-controlled were prepared.Adding acidity and alkaline substance to matrix could transform release behavior.Acidoid can promote release;alkaline substance made release have lag time phenomenon.RP-HPLC method with UV detector was performed to detect the concentration of Dipyridamole in plasma of dogs.Original solution extraction method was using to extract Dipyridamole in plasma. Pharmacokinetics of sustained release pellets of membrane-controlled in dogs hints that Dipyridamole is not suitable to prepare common sustained-release pellets.Because of poor solubility of Dipyridamole in intestinal juice,absorb in vivo is limited.To elevate bioavailability, gastric retention beads were prepared.Gastric floating sustained-release beads were prepared with octadecanol,carbomer.Considerable octadecanol can make beads floating. When pH in gastric juice was higher due to food,age,drug,carbomer was swelling gradually,the corrosion of deads promote dissolution and absorption of Dipyridamole.The release behavior was different in various dissolution media.The plasma concentration of Dipyridamole in dogs were test after a single oral administration of commercial tablets as a reference preparation and floating beads.C_max,T_max,AUC and MRT of commercial tablets and floating beads were(2.23±0.3)μg·mL^-1,(1.28±0.3)μg·mL^-1,3 h, (3.8±3) h,(10.39±0.54)μg·mL^-1,(11.90±0.58)μg·mL^-1,(6.4±0.8) h,(9.8±0.8) h,respectively.Compared with commercial tablets,the relative bioavailability was 118%.The results showed that floating sustained release pellets could raise bioavailability of Dipyridamole.