Quality Evaluation Of Huangyangning Tablets And Analysis Of Key Elements For Its Dissolution In Vitro

Objective: The aim of this study was to establish an analysis method of cyclovirobuxin D in vitro and to evaluate the quality of Huangyangning tablets(nine batches,three manufacturers).Most importantly,clarify the key Elements for its dissolution in vitro,so as to provide theoretical reference for the preparation and quality evaluation of Huangyangning tablets.Methods: A high-performance liquid chromatography coupled with evaporative light scattering detection(HPLC-ELSD)method was developed and a complete methodological evaluation was established through literature investigation and experimental exploration.The quality of Huangyangning tablets was evaluated by tablet weight difference,hardness,fragility and other indicators.The content and content uniformity of Huangyangning tablets were determined by the developed HPLC-ELSD method.The in vitro dissolution experiment was carried out by the small cup method to investigate the dissolution consistency of Huangyangning tablets in vitro.The crystal forms of Huangyangning tablets and APIs from different manufacturers were studied by powder X-ray diffraction(PXRD),infrared spectroscopy(IR),and differential scanning calorimetry(DSC).The DSC and HPLC-ELSD methods were used to evaluate the compatibility of the tablet excipients.Huangyangning tablets were prepared by wet granulation and compression method.The fluidity of the particles was evaluated by fluidity index method.The effect of the types of adhesives and disintegrants on drug dissolution was investigated by dissolution curve comparison method.Results: The HPLC-ELSD technique was carried out using a Luna C18 column(250 ×4.6 mm,particle size,5 ?m)with a gradient elution of 0.1% formic acid in ammonium formate-acetonitrile as the mobile phase.The detector was Waters ELSD 2424(drift tube temperature: 60?,nitrogen pressure: 25 psi).The tablet weights differences met the requirements.The hardness ranged from 1.2 to 4.4 kg,and the fragility met therequirements,too.The contents of tablets were 73%-78%,68%-83% and 93%-97% of the labeled amount,respectively.The content uniformity of the dispersible tablets conformed to the regulations,while the common tablets did not meet the regulations.The in vitro dissolution of Huangyangning tablets from different manufacturers was inconsistent.The APIs were all of the same crystal form and the crystal form of common tablets was the same as that of the APIs,while the drug in dispersible tablets was amorphous form.The drugs in the self-made tablets had good compatibility with the excipients.The drug content of self-made tablets was lower than the theoretical value,but other indicators were qualified.All self-made tablets had the same crystal form as the APIs.The effects of different adhesives and disintegrants of tablets were also different in vitro dissolution.Conclusions: A simple,rapid,sensitive and accurate HPLC-ELSD method is established for the quantification and dissolution of cyclovirobuxine D in huangyangning tablets.The different manufacturers of huangyangning tablets have different dissolution in vitro.PXRD,IR,DSC can be used to determine the crystal form of drugs.Different formulations of pharmaceutical preparations may have different effects on their dissolution in vitro.