Aspirin Dipyridamole Sustained-release Capsules

Aggrenox is an effective combination antiplatelet agent which contains dipyridamole in an extended-release form and aspirin in an immediate-release form. The combination has been marketed in many countries since it was approved by FDA in the end of 1999. Its curative effect is twice more than that of each component, respectively. The compound sustained-release capsules of twice daily administration were designed and prepared with reference to the foreign product.According to the literature, high-performance liquid chromatography (HPLC) method was developed for determination of content and ultraviolet (UV) spectrophotometry method was developed for determination of drug release, respectively.Dipyridamole pellets, whose content was about 85%, were prepared by means of powder layering by the centrifugal coating and granulation equipment. Eudragit^?NE30D and Eudragit^? L30D-55 were used as coating materials. The effects of process variables and formulation variables on coating pellets preparation were investigated. The results showed the coated pellets had a marked sustained-release property. The description of release profiles suggested that the first-order became the most appropriate model to describe release kinetics.Aspirin tablets in an immediate-release were prepared by direct compression method, Aspirin in the tablets released quickly and accord with the regulation.A bioequivalence assessment was conducted for a compound extended-release dipyridamole/aspirin capsule compared with the marketed immediate-release dipyridamole tablets and enteric-coated aspirin tablets administered simultaneously after single- and multiple-dose administration in fasting, healthy, Chinese male subjects. The plasma concentration of dipyridamole and aspirin were determined by HPLC-UV method, respectively. For the single-dose study, the AUC_0-24 of the dipyridamole in the test preparation was (12010.2±5218.6) ng·h·mL^-1 and the AUC_0-12 of reference preparation was (8543.7±3190.4) ng·h·mL^-1, and the mean relative bioavailability of dipyridamole was (108.4±33.7)%. The AUC_0-12 of salicylic acid of the test preparation was (6632.2±1559.8) ng·h·mL^-1 and the AUC_0-12 of reference preparation was (7058.8±1485.3)ng·h·mL^-1, the mean relative bioavailability of salicylic acid was (95.4±18.1)%After repeated oral the test preparation and the reference preparation, the relative bioavailability of dipyriadmole of the test preparation was calculated to be (97.22±32.5)%. the relative bioavailability of salicylic acid of the test preparation was calculated to be (96.7±11.7)%. The results indicated that test preparation was bioequivalent to the reference preparation.