尼莫地平-PVP共沉淀物对药物由制剂中溶出的影响

 目的:提高难溶性药物尼莫地平的溶解度,并在此基础上研制出其速释制剂。方法:选用PVP-k₃₀为载体制备了尼莫地平的共沉淀物与机械混合物,比较了二者体外药物溶出度及药物的结晶形态,并考察共沉淀物的稳定性,进而对尼莫地平速释片剂处方进行筛选,按最优处方制备胶囊剂。比较自制速释胶囊剂与市售片剂的释药情况。结果:尼莫地平由共沉淀物中的溶出度大大高于机械混合物,5min的释药量,前者为89%,而后者仅为45%。X-射线衍射实验表明,尼莫地平在以PVP为载体的共沉淀物中是以非晶体形式存在,放置一年后无结晶出现。结论:将尼莫地平制成PVP共沉淀物,进而制成片剂或胶囊剂,其药物溶出度较普通片剂大为改善,提高了生物利用度。

Enhanced dissolution of nimodipine from the preparations of the drug-PVP precipitates

OBJECTIVE: To enhance the dissolution rate and efficacy of nimodipine (NMDP) which is a poorly water soluble substance, and to design the formulations with fast release properties. METHOD: NMDP PVP k 30 coprecipitate and physical mixture were prepared. The physical states of NMDP in both newly made and one year old samples were investigated by X ray diffraction analysis. The dissolution rates of NMDP from coprecipitate and from physical mixture were also compared. Five formulations were prepared on the basis of NMDP PVP k 30 coprecipitate and their in vitro drug dissolution behaviors were examined. Also, the dissolution property of the capsules with one selected composition was examined. The selected capsules were compared with two commercial tablets on their drug release processes. RESULTS: NMDP PVP k 30 coprecipitate gave much higher improvement in the dissolution rate than the physical mixture, and NMDP was released 89% from the coprecipitate and 45% from the physical mixture in five minutes respectively. There was no appearance of crystallization in the coprecipitate after one year storage under experimental conditions. The tablet formulation with the highest drug dissolution rate was selected. The capsules with the same composition as the selected tablet showed a higher drug dissolution rate, which indicated that drug release property was influenced by the compressing pressure. The results showed that the dissolution rate of NMDP from the selected capsules was about three to four times of that from the two commercial tablets.CONCLUSION: The dissolution rate of NMDP can be improved greatly by coprecipitation using PVP k 30 as a carrier.