Study On The Quality Evaluation Method Based On Danggui Buxue Tablets

Danggui Buxue Decoction was first published in"Discourse on Internal and External Injuries"by Li Dong Yuan,one of the four great masters of Jin Yuan,this formula consists of only two medicines,Danggui and Huangqi,and is a representative formula for tonifying blood and benefiting qi.The former is the first medicine to nourish blood,and the latter is the longest tonic;Danggui is the sacred medicine of gynecology,and is known as"nine gui in ten prescriptions",while Huangqi is the king of qi tonic,and is the qi medicine of blood;the formula emphasizes the use of Huangqi to nourish the qi of spleen and lung,in order to fund the source of blood production,with Danggui to benefit the blood and combine with Ying,so Danggui Buxue Decoction is of great research value and significance.Danggui Buxue Decoction is currently included in the 2020 edition of the Chinese Pharmacopoeia in the form of Danggui Buxue Oral Liquid,which means that the only two popular formulations of this formula on the market are the ancient soup and the oral liquid.Liquid formulations have their own limitations,while tablets are widely used because of their inherent advantages such as accurate dosage,ease of administration,stable quality,and convenient transportation and storage,as evidenced by their proportion in the pharmacopoeia.Therefore,this research topic focuses on the development of Danggui Buxue Tablet based on the preparation standard of Danggui Buxue Oral Liquid in the 2020edition of Chinese Pharmacopoeia,and the following three aspects will be studied.1.Extraction process optimization study1.1 Extraction process optimization of Danggui sinensis volatile oilAlthough Danggui sinensis is a ministerial medicine,its pharmacological effects and adjuvant effects are significant.As an aromatic herbal medicine,the role of Danggui volatile oil cannot be ignored.The extraction time(A),material-to-liquid ratio(B)and soaking time(C)of the three key influencing factors in the extraction process of Danggui volatile oil were determined by single-factor investigation,and then the response rate of Danggui volatile oil extraction((m volatile oil/m herb)×100%)was used as the response value.The extraction process of Danggui volatile oil was optimized by using Box-Behnken response surface method in Design-Except version 12 software,and the best extraction process was finally determined as 8.65 h extraction time,1:10 material-liquid ratio,1.77h soaking time,and the extraction fitted equation:Y=0.584375+0.05677A-0.057031B+0.442708C+0.004688AB+0.01875AC+0.015625BC-0.007943A~2-0.000911B~2-0.214583C~2.1.2 Drying process of Danggui Buxue tabletsThe preparation process of Danggui Buxue Oral Liquid in the 2020 edition of Chinese Pharmacopoeia was combined with the preparation process of Danggui Buxue tablet prescription in advance;three different drying processes of freeze-drying,belt-drying and spray-drying were investigated,and spray-drying was determined as the optimal drying process for the preparation.2.Study on the forming process of Danggui Buxue tablets2.1 Study on the screening of excipients for Danggui Buxue tabletsThe dosage of Danggui Buxue Oral Liquid was used as the standard to determine the dosage requirements of Danggui Buxue Tablets,as well as the amount of infusion and the proportion of excipients in the prescription,based on which the screening of excipients in the molding process was designed and optimized.The comprehensive evaluation criteria were determined,and the optimal ratios of three fillers MCC-101,mannitol and lactose were finally determined using the top design in the mixer experimental design;the types and addition methods of disintegrants were examined;the types of wetting agents and The procedures and methods for the investigation of wetting agents were determined using the torque rheometer MTR-3.2.2 Granulation process of Danggui Buxue TabletsThe applicability of two granulation processes,namely high-speed shear wet stirring granulation and fluidized bed one-step granulation,was investigated for this study,and the best granulation process was determined using high-speed shear wet stirring granulation.2.3 Design and study of high speed shear wet stirring granulation process for Danggui Buxue TabletsBased on the design concept of quality,the study focused on high-speed shear wet agitation granulation.Preliminary screening was performed to determine the level range of seven influencing factors,namely dry mixing time,dry mixing speed,spray pressure,peristaltic pump speed,wet mixing time,wet mixing cutting knife speed and wet mixing paddle speed,and 17 indicators were used as characterization indexes for the pellets,and a Plackett-Burmann experimental design was performed using JMP PRO version 16 software to perform a preliminary screening and optimization of high shear wet stirring granulation The preliminary screening and optimization of the influencing factors were carried out.IBM SPSS Statistics version 21 was used to normalize the 17 indicators of the 12 batches of P.B experimental design as well as principal component analysis to determine Median density and Apparent density Da as the final response values,based on which the P.B experimental results were analyzed to establish the wet mixing time,wet mixing stirring speed and peristaltic pump pump speed as the The key influencing factors were established.Based on the analysis and discussion of the P.B results,the preliminary sieved results were further optimized using the Box-Behnken response surface method.3.Establishment of quality standards for Danggui Buxue tabletsThe characterization,thin-layer identification and check items such as weight difference and disintegration time limit were examined for Danggui Buxue tablets,with emphasis on the establishment of a method for the determination of Calycosin 7-O-β-D-glucopyranoside in Danggui Buxue tablets by high performance liquid chromatography with HPLC and methodological investigation.