基于生物活性测定方法的黄连素固体制剂体外溶出度研究

Research of in vitro Dissolution of Berberine Solid Preparation Based on Biological Activity

目的:探讨符合中医药特点的中药固体制剂质量控制与评价的化学-生物联合评价模式。方法:以复方黄连素片为模型药,考察在溶出介质水中,不同溶出时间的复方黄连素片溶出液对敏感菌的抑制作用,提出基于细菌抑制率所得复方黄连素片的溶出度测定法,并与HPLC法所测的盐酸小檗碱指标成分的溶出度进行f_2相似因子法相关性评价。结果:抑菌实验表明,黄连素对大肠埃希菌、金黄色葡萄球菌、枯草芽胞杆菌、藤黄微球菌和白色念珠菌等多种菌敏感,其中枯草芽胞杆菌的抑菌圈边缘清晰、敏感度较高。以HPLC法所测得的复方黄连素片的溶出曲线为参比,7个不同厂家复方黄连素片的生物效价溶出度曲线相似因子f_2均大于50,说明以生物效价测定法为基础的溶出度能较为全面地反映出复方黄连素片的生物利用度。结论:以生物活性为基础的溶出度评价方法有望成为评价中药固体制剂体外溶出度的有效手段之一。

Objective： To explore the chemical and biological assay pattern for the quality control and evaluation of Chinese materia medica solid preparations（ CMMSP）. Methods： Compound berberine tablets were used as the model drug,the inhibition against sensitive strains of the dissolution solution at different time points was studied with water as the dissolution medium,and the cumulative dissolution of compound berberine tablets was obtained based on the bacterial inhibitory rate. The dissolution of hydrochloric acid berberine was also determined by HPLC,and a f_2 similar factor method was used to evaluate the relevance of the two methods. Results：The antimicrobial test showed that berberine was sensitive to escherichia coli,staphylococcus aureus,bacillus subtilis,micrococcus luteus and candida albicans etc,and among them,the antibacterial circle edge of bacillus subtilis was clear with higher sensitivity. The dissolution curve of compound berberine tablets determined by HPLC as the reference,the similarity factor f_2 of bio-dissolution curve of compound berberine tablets from 7 different manufactures was greater than 50,which suggested that the dissolution determination method based on biological titer determination could comprehensively reflect the bioavailability of compound berberine tablets.Conclusion： The biological activity evaluation method for dissolution is expected to be one of the effective means for in vitro dissolution test of CMMSP.