| Objective:Yinzhihuang preparation is composed of Artemisiae capillaries,Gardenia jasminoides Ellis,Lonicera japonica and baicalin.Its major functions are heat-clearing, detoxication,promoting urination and retreating jaundice.It is usually used for the syndrome of hepatochlic hygropyrexia.Yinzhihuang preparation's traditional dosage forms are oral liquid and injectable preparation,but there are shortages of nonconvenient taken for oral liquid and more adverse effects for injectable preparation.Dispersible tablet is a dosage form of quick disintegrate and uniform disperse in water.It was proved that Yinzhihuang dispersible tablet can improve bioavailability and degrade adverse effects.This topic applied modern technology for Yinzhihuang dispersible tablet to research the part of pre-clinical PHARM.Methods:Extraction of Artemisiae capillaries:①To determine total flavonoids by UV and use rutin as control article.②To optimize the extraction technology by orthogonal design in the base of single factor investigation.Extraction of Gardenia jasminoides Ellis:①To determine by HPLC and use jasminoidin as control article.②To optimize the extraction technology by orthogonal design in the base of single factor investigation.Extraction of Lonicera japonica:①To determine by HPLC and use caffeotannic acid as control article.②To optimize the extraction technology by orthogonal design in the base of single factor investigation.Preparation of Yinzhihuang dispersible tablet:①To bolt adjuvants by single factor investigation through investigating shaping efficiency,dispersion unif,disintegration time and so on.②To optimize the formula by orthogonal design through investigating disintegration time.Quality criteria of Yinzhihuang dispersible tablet:It is including discrimination, assaying,dispersion unif,dissolution and so on.Initial stability investigation of Yinzhihuang dispersible tablet:To investigate the influence of temperature,humidity and illumination to Yinzhihuang dispersible tablet in influential factor experiment.To contrast the pharmacokinetic of Yinzhihuang dispersible tablets and conventional tablets in vivo of Beagle dog.Results:Extraction of Artemisiae capillaries:①The linear correlation was fine within 18.29～91.44μg·mL-1 about rutin.RSD%of method precision was 0.90%.The average of spotting recovery rate were 100.4%,100.9%and 98.7%in low,middle and high group.This method can be used for quantitation of total flavonoids in Artemisiae capillaries extractive.②The optimized extraction technology was obtained as follows:the concentration of alcohol was 50%,the volume was 10 times,the recirculation time was 1.5h,and extracted for 3 times.Extraction of Gardenia jasminoides Ellis:①The linear correlation was fine within 0.0238～0.2618μg about jasminoidin.RSD%of method precision was 0.98%.The average of spotting recovery rate were 99.7%,98.1%and 100.4%in low,middle and high group.This method can be used for quantitation of jasminoidin in Gardenia jasminoides Ellis extractive.②The optimized extraction technology was obtained as follows:the concentration of alcohol was 70%,the volume was 8 times,the recirculation time was 2h,and extracted for 3 times.Extraction of Lonicera japonica:①The linear correlation was fine within 0.01024～0.512μg about caffeotannic acid.RSD%of method precision was 1.26%.The average of spotting recovery rate were 99.2%,100.9%and 101.2%in low,middle and high group.This method can be used for quantitation of caffeotannic acid in Lonicera japonica extractive.②The optimized extraction technology was obtained as follows:the extraction dissolvent was water,the volume was 15 times,the decoction time was 30min,and extracted for 3 times.Preparation of Yinzhihuang dispersible tablet:①The result of single factor experiment demonstrated that the best prescription was composed of PVPP and CCNa for disintegrants,MCC for bulking agent,50%alcohol for wetting agent and magnesium stearate for lubricant.②The optimized formula comprised 10% PVPP,6%CCNa and 40%MCC by orthogonal design.③The wet granulated pellet method had been applied.The discriminate methods had been made for Gardenia jasminoides Ellis,Lonicera japonica and baicalin.Also,the assay method for baicalin had been made by HPLC,this method was accurate,sensitive and fine reproducibility.There were satisfactory linear correlations for concentration and peak area,besides,the adjuvants had non-interference for assaying.Yinzhihuang dispersible tablet can disintegrate within 3min,and can go through the sifter of number 2 after disintegration.The dissolution can exceed 85%in 2min.It had been demonstrated that Yinzhihuang dispersible tablet can be effected greatly by high temperature and high relative humidity,but highlight seemed that had little effect.It had been manifested that AUC(0-24) were(9.829±0.213) and(6.722±0.137) mg·L-1·h,Cmax were(2.442±0.079) and(1.055±0.054) mg·L-1,Tmax were(2.075±0.192) and(4.083±0.209)h for Yinzhihuang dispersible tablet and conventional tablet.The relative bioavailability of Yinzhihuang dispersible tablet was 146.2%by contrast with conventional tablet.In conclusion,dispersible can disaggregate quickly and enhance bioavailability obviously.Conclusion:The effective components in extractives had high contents and high purity by established extraction methods.Yinzhihuang dispersible tablet can release medicine quickly,which had been authenticated by dissolution and pharmacokinetics experiments.The established quality criteria can control the extraction of medicinal substances,manipulate the quality of preparation,and ensure the therapeutic effect of medicine.Yinzhihuang dispersible tablet which had been prepared by optimized technology was a secure and effective dosage form,so it had a satisfactory perspective for exploiting and applicating.
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