Research On The Improvement Of Production Process Of Compound Shuanghua Oral Liquid

Objective:There are three problems need to be solved in the actual production process of the Fu-fang Shuanghua Oral Solution.Firstly,the level of chlorogenic acid,the quality control indicator of the product,is lower than 1 mg·mL-1 standard value after the original processing techniques.Secondly,Fu-fang Shuanghua Oral Solution will produce some black sheet precipitations without diffusing after shaking.At last,Fu-fang Shuanghua oral formulation contains a lot of Andrographis paniculata and a large number of alkaloids,causing bitterness in the throat after patients taking the solution,and the bitterness cannot be dispersed for a long time,patients'compliance are seriously affected.Therefore,according to the manufacturer claims,this study will achieve the following objectives:(1)chlorogenic acid(CA)content,the quality control indicator,in the actual production process should be tracked comprehensively.An on-line near infrared(NIR)spectroscopy monitoring method with an appropriate multivariate calibration method should be developed for the extraction process of Fu-fang Shuanghua oral solution.(2)A reasonable extraction process route should be developed.(3)The causes of the precipitations should be found and the chitosan flocculation technology should be used to improve its clarity.(4)Some flavoring agents should be added to improve the taste of the Fu-fang Shuanghua Oral Solution.Methods:(1)The transfer rates of chlorogenic acid of various procedures of the production process were investigated,and the transfer rates of chlorogenic acid of boiling the formulae in different amounts of water were investigated.During the extraction process,the feasibility of NIR spectroscopy was employed to determine the concentrations of chlorogenic acid content,total phenolic acids contents(TPC),total flavonoids contents(TFC)and soluble solid contents(SSC).High performance liquid chromatography(HPLC),ultraviolet spectrophotometric method(UV)and loss on drying methods were employed as reference methods.Applying of on line NIR in monitoring the extract process of FSOS and determining TPC,TFC,CA and SSC concentrations during the extraction process and the moving block standard deviation(MBSD)method was used to evaluate the ending point.(2)Single factor method was used to choose the optimal alcohol concentration and orthogonal screening method was used to optimize the parameters of alcohol extract of Lonicera japonica using transfer rate of chlorogenic acid as the indicator.A suitable extraction process route of boiling Andrographis paniculata,Forsythia suspense and Radix Isatidis was preferably chosen using(R.S)-epigoitrin transfer rate as an indicator.And orthogonal method was used to screen the alcohol precipitation process parameters using the(R.S)-epigoitrin transfer rate,protein clearance,tannin clearance,polysaccharides clearance and ratio of extraction as indicators.The parameters of other procedures were preferably chosen.(3)Single factor screening methods were applied to screen the coagulant dosage,solution concentration,coagulation temperature,flocculation time and speed using the color of the liquid,the amount of the precipitations,filtering degree and turbidity(NTU)as indicators.And based on the results of single factor screening methods,17 test point response surface analysis experiments were experimented according to the principle of optimization Box-Behnken to optimize flocculation conditions using retention of chlorogenic acid,proteins,tannins,polysaccharide content and turbidity as the indexes.(4)Single factor screening methods were applied to screen the amounts and kinds of sweeteners,sour agents and essences based on the results of scores of different individuals,Fuzzy Mathematics was used to evaluate the optimal taste-modifying prescriptions.Results:(1)The results showed that transfer rate of chlorogenic acid in the extraction was lower than 50%,indicating that the extraction process parameters was unreasonable and needed further optimization.Transfer rates of chlorogenic acid in the 6,8,10,12,15-fold amount of water were also lower than 50%.On-line near infrared technology and moving block standard deviation(MBSD)method were used to monitor the extraction process and evaluate the ending point and proved that the extraction time is too long,resulting in a substantial decline in its quality control content of chlorogenic acid,which is a waste of resources and energy,so the process needed further improvement.(2)Lonicera japonica was extracted 2 times with 8-fold of 60%ethanol,0.5 hours for each time.Chlorogenic acid transfer rate was up to 87.59%.The other three were extracted 2 times with 12-fold of water for each 1.5 hours,and(R.S)-epigoitrin transfer rate was up to 77.54%.The ethanol precipitation process parameters were as follows:concentrated liquid density of 1.00 to 1.05,alcohol content of 80%,to stand for 12 hours and deposited with alcohol,(R.S)-epigoitrin transfer rate was 68.77%,protein clearance rate was 67.70%,tannin clearance rate was 48.52%,polysaccharides clearance was 70.66%.(3)The optimal flocculation conditions were:chitosan in an amount of 17 mL(per 100mL concentrated liquid),liquid concentrate density of 0.2 g·mL-1,the flocculation temperature of 55?.(4)The optimal formula ingredients were as follows:3 mg·mL-1 acesulfame,3 mg·mL-1 aspartame,5 mg·mL-1 citric acid and 5 mg·mL-1 peach flavor.The taste-modifying prescriptions provide great value for further scale production.Conclusions:the contents of chlorogenic acid in the original production process were comprehensively tracked.On-line near infrared technology and moving block standard deviation(MBSD)method were used to monitor the extraction process and evaluate the ending point.The varing pattern of the content of chlorogenic acid had been mastered.The clarity of FSOS was improved by adding chitosan flocculation.The taste of the FSOS had been improved by adding flavoring agents.All the above provide a large number of reliable test data and experimental basis for modifying the production process.