The Study Of The Preparation And Stability Of L-carnitine Oral Liquid

Objective:L-carnitine is a kind of amino acids to promote fat transformed into energy,no bad reaction to the human body.It is a natural,the body fat metabolism necessary internal material.Because L-carnitine to the animal body fat metabolism and energy supply plays an important role,once the animals because of the synthesis of carnitine in the body is blocked or carnitine excessive discharge and degradation,or activity of carnitine transfer system decreased and the loss and so on,can cause the body lipid metabolism disorder,energy supply,and triggered a series of related diseases.The oral liquid formulations have the advantages of meet clinical needs,easy to accept with patients and dose accurately.With the development of science,its application prospect will be more widely,because the production method is simple,therefore has the possibility of industrial production.This topic proposed to develop L-carnitine oral liquid,to set up oral liquid intestinal absorption model,quality control standards,examine its stability,and predict its validity in room temperature.Methods:The composition of the control formula was first carried out the initial screening of accessories.During single-factor test,we select suitable pharmaceutical excipients and preparation method.Again according to the results of screening,select a large influence on several factors,orthogonal experimental design L9(33),choose the right amount to get the final optimal prescription.According to the references,we select suitable method for quality control and quality inspection.Reference to "the State Food and Drug Administration guidelines for stability of new drugs" and the actual situation,we conduct the stability tests,to inspect the stability of bulk drugs and formulations in the strong acids,alkalis,oxidizing conditions,the influence of the preparation by strong light,high temperature,and part of long-term tests.Adopt clean male SD rats in vitro intestinal circulation experiment,examine drug absorption of the duodenum,jejunum,ileum,calculate the absorption rate constant(Ka)and absorption coefficient(Papp),Used the completely random design analysis of variance,examine whether the drug absorption between different intestinal segments have significant difference;Drug concentration changes of high,medium and low three under the concentration of all rats intestinal drug absorption,drug absorption rate constant and absorption coefficient calculation,Uses the completely random design analysis of variance,between different drug concentrations under investigation in the whole intestine absorption examine whether it is have significant difference.Constant temperature accelerated test to select 60,70,80,90 ? four constant temperature for water bat,according to the design of experiment time sampling,using high performance liquid chromatography(HPLC)method to calculate its concentration in different temperature and different time,using classical constant temperature method,according to the Arrhenius formula,with relative mass fraction of plotting logarithmic(IgC)on time(t),get a different temperature of regression equation and the decomposition rate constant,calculates its validity under room temperature(25 ?);Using multiple linear regression model,using the statistical software SPSS 17.0,to In(lnCO-InC)multivariate linear regression with 1/T,getting regression equation,calculate its validity under room temperature(25 ?).Compare two methods of calculation result,it is concluded that the validity of L-carnitine oral liquid.Results:In this assay,we filter out the optimization of L-carnitine oral liquid preparation prescription:10 ml solution containing the main medicine tartaric acid L-carnitine 3.6383 g,aspartame 200 mg,strawberry flavor 6 mg.Preparation method is:tartaric acid L-carnitine soluble in 10 ml of water first,then excipients aspartame,strawberry flavor to dissolved respectively,finally packaging sterilization.HPLC method reliable stability by the methodology validation.Determination choice of RP-HPLC,the mobile phase of 0.05 mol-L-1 potassium dihydrogen phosphate solution(80%phosphoric acid to adjust PH to 2.4):methanol = 95:5,velocity:0.5 mL-min"1,detection wavelength:225 nm,column temperature:room temperature,sample quantity:20 ?L.Measured during preparation of small batch preparation,content is 90.0%?110.0%of labeled amount.The drugs bulk drugs and formulations stable under the condition of strong acid,strong alkali and strong oxidizing are unstable.The result shows that high temperature and strong light have no influence to L-carnitine oral liquid.Rat intestinal absorption test the Ka values under different intestinal segments of variance analysis results show that the P>0.05,the duodenum,jejunum,ileum,there was no statistically significant difference of Ka values,different bowel has no effect on the absorption rate constant;Ka values under different concentrations of variance analysis results show that the P>0.05,the concentration of drugs there was no statistically significant difference values of Ka,concentration has no effect on the absorption rate constant.Classical constant temperature method is used to draw the validity of the drug at room temperature was 3.19 years;And the use of multiple linear regression model,and it is concluded that the validity of the drug is 3.49 years,the results of the two methods are basically identical.Conclusion:This topic selected optimization of L-carnitine oral liquid preparation of prescription,the preparations of character is good,the indicators meet the requirements.Quality control method for a good specificity,easy to use,can be used for content determination of the drug.Stability test can provide basis for the establishment of the period of validity for drugs.