Research On The Taste-masking Prescription And Stability Of Xiaoer Ganmaoning Oral Liquid Based On Multiple-indicator Evaluation

Objective:This study intended to optimize the prescription to improve the odor and taste of the preparation by using cyclodextrin inclusion,taste-masking and image processing techniques under the premise of not affecting the stability of the Xiaoer Ganmaoning Oral Liquid,and then improve the patient compliance.Methods:1.Gas chromatography（GC）method was established to measure the components of menthol,menthone and pulegone in EOs.Based on the single-factor test,agitation was applied to prepare EOs cyclodextrin inclusion and the preparation process was optimized by Box-Behnken Design experiments（BBD）that cyclodextrin-to-oils ratio,the concentration of HP-β-CD and temperature were independent variable respectively,while the comprehensive scores of oil content in inclusion,encapsulation efficiency and yield as a dependent variable.2.On the basis of preliminary screening of the types and dosage of flavoring agents by using artificial and supplemented electronic tongue evaluation,the prescription of flavoring agents was optimized by fuzzy mathematics and orthogonal experimental design methods,and the dosages of neotame,hesperidin dihydrochalcone（NHDC）and Na Cl were independent variable,while the comprehensive score（S₂）of the taste of preparation was taken as the dependent variable.3.The influence of different taste-masking prescriptions on the stability of Xiaoer Ganmaoning Oral Liquid was investigated by using filtration and image processing technique which based on Matlab,and the final optimising prescription was clarified to conduct a pilot scale-up study.4.The high performance liquid chromatography（HPLC）characteristic spectrum of Xiaoer Ganmaoning Oral Liquid was established,and the attribution of original herbs as well as the index component of characteristic peaks,the range of similarity with the reference map were clarified.Results:1.The optimum conditions for inclusion process were as follow:the ratio of cyclodextrin-to-oils was 11:1,the concentration of HP-β-CD was 40%,the temperature was 47℃,the inclusion time was 1.5h and the stir speed was 600 r/m,and the comprehensive scores was 83.24 in this condition.Proven experiment shows that the difference ratio that between predicted value and actual value was just 1.09%and the process which optimized by response surface method of EOs inclusions was feasible and stability.2.The results of artificial and electronic tongues was consistent,and the optimising program of flavoring agents were 0.0084%neotame,0.0028%NHDC,0.24%Na Cl and 0.1%FC-03027 sweet orange liquid flavor.3.Compared with the original process group,the optimising prescription had little effect on the stability of Xiaoer Ganmaoning Oral Liquid under the refrigeration,room temperature and accelerated experiment conditions（P>0.05）.4.The results showed that the similarity between the 10batches of Xiaoer Ganmaoning Oral Liquid and the reference feature map was higher than 0.994.18 characteristic peaks were assigned,it’s individually derived from different medicinal herbs included Scutellariae Radix,Arctii Fructus,Lonicerae Japonicae Flos,Gardeniae Fructus,Forsythiae Fructus,etc.And 11 characteristic peaks were assigned by the reference substance and identified as chlorogenic acid,neochlorogenic acid,cryptochlorogenic,isochlorogenic acid A,isochlorogenic acid C,baicalin,sbaicalein,wogonin,scutellarin,forsythiaside A,arctiin.On that basis,the characteristic spectrum of precipitate in the Mixture was established,and the similarity between the 10 batches of precipitate and the reference feature map was higher than 0.940.Compare with the characteristic spectrum of the Mixture,it was found that 14 characteristic peaks in the characteristic spectrum of precipitate has the similar retention time,and the index compounds content was lower than 5%.Conclusions:The poor taste of bitterness and irritation in Xiaoer Ganmaoning Oral Liquid was concerned,so that the volatile oil was prepared by cyclodextrin inclusion technology firstly,and it was effectively improved by adding appropriate flavoring agents such as neotame,NHDC and Na Cl.Also,the stability of the preparation was investigated combined with Matlab digital image processing technique to optimize the final optimising prescription.Moreover,the HPLC characteristic spectrum of the mixture and its precipitate was established to improve the quality standard of Xiaoer Ganmaoning Oral Liquid,so the research goal of the subject was achieved.