Compound Dipyridamole Sustained-release Capsules

Both dipyridamole and aspirin are anticoagulant drugs. According to recent reports, 25 mg rapidly release aspirin and 200mg extended release dipyridamole used two times per day can lower the rate of suffering strokes. So in this paper the pharmaceutics was studied in detail.According on the characteristics of releasing and physical chemistry properties of dipyridamole, we established a reasonable and convenient analytic method at first. Then we studied the solubility and intrinsic dissolution rate of dipyridamole in buffers with different values of pH. The result revealed that the solubility and intrinsic dissolution rate of dipyridamole changed as the value of pH in buffers varied.Based on the above foundation, we carried out the basic research on the extended release gel tablets of dipyridamole, and the formula for studying the in vitro-in vivo correlation was decided. At the same time the dissolution of extended release tablets in different buffers was studied, and it was found that the releasing mechanism of the extended release tablets was through both corrosion and diffusion. The drug release of the extended release tablets was quick in the gastric juice mainly through corrosion and slow in the intestinal juice mainly through diffusion.We chose a proper method for analyzing drug concentration in vivo of dogs, and then established a suitable dissolution condition in vitro: in the first 2 hours the dissolution was proceeded in the pHl .3 buffer, and in the rest 8 hours the dissolution was proceeded in the pH5.8 buffer.Based on the dissolution properties of the extended-release tablets of dipyridamol, we studied the coated pellets of dipyridamole. By statistical analysis of the release curves of capsules that consisted of coated pellets of dipyridamole and aspirin pellets, we found that there was no significant difference between the releaseof compound preparation and that of individual preparation.The study on complex extended release capsules of dipyridamole in vivo of dogs showed that Tmax of extended release capsules(5.46±0.53hr)was longer than conventional tablets(3.19±0.21hr). The Cmax of conventional tablets wasl.46± 0.03 u g/ml ,and the Cmaxof extended release capsules wasl.35 ± 0.02 u g/ml. The AUCo- between conventional tablets (28.13 ± 0.93 u g-hr/mi)and extended release capsules(31.73± 1.03 u hr/ml) was coincident. Through calculation, the relative bioavailability of dipyridamole and aspirin in the capsules were 112.8% and 102.8% respectively. The correlation study showed that a good relationship between in vivo and in vitro was built.