尼可地尔口腔速溶片的研究(英文)

PHARMACEUTICAL EVALUATION OF FAST DISINTEGRANT TABLET CONTAINING NICORANDIL LOADED PARTICLES

目的 制备尼可地尔口腔速溶片以提高其生物利用度和改善药物的苦味。方法 用croscarmellosesodium ,D 甘露醇和乳糖制备直径为 6mm(崩解时限为 12s)和 10mm(崩解时限为 2 3s)的尼可地尔口腔速溶片。对其崩解性能、硬度、药物释放度、体内吸收及口感性能进行了考察。结果 压力在 1 37× 10 8Pa以上 ,甘露醇 乳糖比为 9∶1,croscarmellosesodium的添加量为 1% - 4%时 ,口腔速溶片的崩解时间较市售片缩短了 1 3,且能达到一定的硬度。对Beagle犬经口服给药后 ,测得血药浓度与市售片相同 ,AUC ,Cmax,Tmax值无明显差异。口腔速溶片有长效和掩盖药物苦味的作用 ,同时甜味剂对掩盖药物苦味有相加作用。结论 口腔速溶片为快速崩解型片剂 ,与市售片等效 。

AIM To improve the bioavailability and taste of fast disintegrating tablet (FD tablet) containing nicorandil loaded particles. METHODS A FD tablet containing nicorandil loaded particles with 1%-4% croscarmellose sodium in addition of D mannitol and lactose (9∶1) was prepared and the dissolution and absorption characteristics were examined, in comparison with FD tablet and commercial tablets of nicorandil. In vivo absorption of nicorandil from FD tablet was evaluated in beagle dogs. RESULTS The disintegration time of FD tablets containing 1% croscarmellose sodium with 6 mm and 10 mm in diameter were about 12 and 23 seconds, respectively. When nicorandil loaded particles consist of myristyl alcohol and stearyl alcohol were put in FD tablet, nicorandil release from FD tablet continued until 6 h while nicorandil release from Sigmart and FD tablet containing nicorandil crystals finished within 5 min. In vivo absorption of nicorandil from Sigmart and FD tablet containing nicorandil crystals was very similar after oral administration in beagle dogs and no statistic difference in AUC, T max , C max was observed between these tablets. However pharmacokinetics parameters of nicorandil after oral administration of FD tablet containing nicorandil loaded particles showed that nicorandil was delivered into the body at a suitable absorption rate with similar AUC, delayed T max and lower C max . CONCLUSION The reports suggest that the modification of properties of myristyl alcohol and stearyl alcohol released from the drug loaded particles system would lead to more acceptable bioavailability of the system. However, The formulation of particles and may have a masking effect against the bitter taste and irritation of the drug.