The Preparation Process And Quality Research Of Vitamin B₂ Immediate Release Tablets

Vitamin B₂ plays an important role in the process of biological oxidation in human body.Its tablet was first marketed in China in 2002.The prescription process was relatively old,and the pharmacopeia of various countries had very different standards for their quality evaluation.To adapt to market changes and improve the quality of tablets,this article took the slightly soluble drug Vitamin B₂ as the target,according to the properties of each excipient material,Vitamin B₂ immediate release tablets under the new prescription and preparation process were studied.Through the comparison of domestic and foreign pharmacopoeia standards,a new method was established for the evaluation of in vitro dissolution,content and related substances of tablets.The newly established quality evaluation method makes up for the deficiency of the current quality evaluation and improves the current quality standard of this tablet.In this paper,the newly established tablet preparation process and quality analysis method have been used as the official materials for a domestic pharmaceutical manufacturer to declare the consistency evaluation of generic drugs.At the same time,the tablets produced by the new preparation process has realized the mass production in the pharmaceutical company.The detection method of in vitro dissolution,content,and related substances of Vitamin B₂ immediate release tablets was established.The dissolution was determined by the paddle method at a speed of 50 rpm,the dissolution medium was p H 1.2,p H 4.0,p H6.8,and water?900 m L?,and the detection wavelength was 267 nm.The content and content uniformity of the tablet were determined by high performance liquid chromatography?HPLC?,the mobile phase was 0.1%phosphoric acid-acetonitrile?86:14?,and the detection wavelength was 267 nm.HPLC gradient elution was used to determine the relevant substances in tablets.Welch Ultimate AQ-C18 column?4.6 mm×25 0mm,5?m?was used as the chromatographic column.Mobile phase A was 0.1%aqueous phosphoric acid solution,and mobile phase B was acetonitrile.The flow rate was 1.0m L·min^-1,detection wavelength was 267 nm,and column temperature was 30?.The results of methodological verification show that the dissolution experiment method described in this paper has some distinguishing power.Each newly established detection method has the advantages of strong specificity,high accuracy,and good repeatability.It can clarify the four known impurity types and limit requirements,and it can provide an effective method for the screening of tablet prescriptions and preparation processes,quality testing,and stability experiments.In this subject,the types of excipient materials,the proportion of main drug and excipient,and the preparation process parameters in the prescription were first investigated by single factor.Then,the Box-Behnken response surface was used for evaluation,and the best prescription and the best process were finally obtained.The prescription is based on weight percentage:the main drug was 5.0%Vitamin B₂,filler materials were 26.0%corn starch and 62.4%lactose monohydrate,disintegrant material was 5.0%croscarmellose sodium?internal and external addition,3:2?,lubricant material was 1.0%magnesium stearate,and corn starch and dextrin were formulated into 2%binder.Used fluidized bed one-step granulation and tableting method,the raw material medicine and corn starch were crushed by a pulverizer at a weight ratio of 1:5.2 for 20 seconds,and added to the one-step granulator together with other auxiliary materials.The temperature of the material was controlled at 35 to 45°C,the moisture content was 2%to 5%,and the hardness was30±10N.Finally,the pilot scale-up of the small-scale prescription process was carried out.Through the quality test and stability test of the pilot test sample,it shows that Vitamin B₂immediate release tablets prepared under the new formulation process has rapid drug release,high product quality,small-batch difference,simple preparation process,and large operability.It provided a feasible experimental scheme and product quality standard for the pharmaceutical manufacturers to enlarge the production.At the same time,this study also provides a reference for the consistency evaluation of Vitamin B₂ tablets in China.