ORAL SUSTAINED-RELEASE CISPLATIN CAPSULE

An oral sustained-release cisplatin preparation was prepared by combin ing microporous water-insoluble pharmaceutical polymer, ethylcellulose , a membrane and a gel-forming polymer, poly(acrylic) acid (Carbopol). As cisplatin is an extremely hydrophilic and small compound, it was d ifficult to control the release rate solely by the micropores on the e thylcellulose capsule. To retain cisplatin within the capsule, gel-for ming polymer was formulated inside the capsule. The release rate of ci splatin was dependent both on the number of micropores of the capsule and the formulated amount of Carbopol. The number of micropores ranged from 20 and 30 to 60, and the formulated amount of Carbopol varied fr om 15 to 100 mg. In-vitro release experiments suggested that the relea se rate decreased as the formulated amount of Carbopol increased when the pore number was 60 and 30. However, when pore number was decreased to 20, the effect of the amount of Carbopol was not clearly observed. In the in-vivo study using rabbits, the sustained-release cisplatin c apsule was evaluated in comparison with solution after oral administra tion of 20 mg drug. With the pore number of 60, C-max was 0.46 +/- 0.0 2 mu g mL(-1) at 4 h and thereafter serum concentrations declined rapi dly. When the pore number was 30, serum cisplatin level-time profiles showed long-acting patterns and AUC was reversely correlated with the formulated amount of Carbopol. C-max and t(max) were 0.41 +/- 0.02 mu g mL(-1) and 3.33 +/- 0.88 h, respectively and 0.23 +/- 0.01 mu g mL(- 1) was obtained at 24 h after oral administration of capsule having 30 pores and 15 mg of Carbopol. We conclude that the possibility of deve loping an oral sustained-release cisplatin preparation is feasible.