基于生物效价评价不同粉碎粒度对复方鳖甲软肝片体外溶出度的影响

Effects of different pulverization fineness on in vitro dissolution rate of Compound Biejia Ruangan Tablet based on biological value evaluation

目的采用MTT比色法从细胞增殖的角度,结合HPLC法,探讨不同粉碎粒度对中药固体制剂体外溶出度的影响。方法以复方鳖甲软肝片为模型药,对其原粉入药的药材进行不同程度的粉碎,考察在pH 7.4 PBS溶出介质中,不同粒度复方鳖甲软肝片溶出液对LX-2肝星状细胞的抑制作用,提出基于细胞抑制率所得复方鳖甲软肝片的累积溶出度,并与HPLC法测定芍药苷指标成分所得的溶出度运用f2相似因子法进行相关性评价。结果芍药苷溶出度随粉碎粒度改变而发生变化,其中200、300目体外累积溶出率较高,且f2相似因子大于50,表明粒度为200、300目时,2种方法所测的溶出度具有较好的相关性。结论基于生物效价检测方法可用于复方鳖甲软肝片的粒度筛选,同时,考虑到实际生产过程中成本因素,确定200目为复方鳖甲软肝片的最佳生产工艺。

Objective To explore the effects of different pulverization fineness of solid preparations of Chinese materia medica on their in vitro dissolution, using MTT method combined with HPLC. Methods Compound Biejia Ruangan Tablet （CBRT） was used as model drug, and MTT method was used to obtain the characteristic cell inhibitory rate by different pulverization fineness of dissolving solutions in the dissolution medium （phosphate buffer, pH value 7.4） at different time points. From these results, the cumulative dissolution of CBRT based on cell inhibitory rate was obtained. The dissolution rates of paeoniflorin was determined by HPLC method. Using f2 similar factor, the relevance of these two methods was evaluated. Results Dissolution of paeoniflorin is changed with the change of pulverization fineness, the accumulative dissolutions of 200 and 300 meshes in vitro were higher than those of other meshes. The results showed that f2 values of 200 and 300 meshes were more than 50, indicating that there was a good correlation between the two methods of measuring the dissolution rate. Conclusion The results show that the biological potency detection could be used to screen the particle size of CBRT. Considering the production cost of CBRT, 200 mesh is the best particle size.