Study On Product Process And Quality Specification Of Cihuangzengdan Powder

Objective:The goal of this study is to develop the extraction and formulation protocol as well as the quality standard of Cihuangzengdan Powder.In addition,the stability of the Cihuangzengdan Powder was also investigated.Our final goal is to provide the required data for the application as a new veterinary drug.Methods:The best extraction time and procedure was developed via comparing the different extraction solvent,solid-liquid ratio and extraction time.Based on the loss rate of the lilacs glycosides combing with the alcohol usage,the best alcohol precipitation protocol was developed including the required concentration of the water-extracted material,duration for the precipitation as well as the added alcohol volume.Based on the content of the lilacs glycosides,the alcohol-extracted Cihuangzengdan Powder was concentrated.The drying protocol was developed via comparing different temperatures,vacuum degrees and moisture levels.The glucose was appropriately added based on the content of the lilacs glycosides,ability to absorb the moisture etc.The quality criteria include drug character observation,TLC analysis for the three components(Acanthopanax senticosus,Astragalus and Angelica),solubility,moisture,evenness in appearance,volume,quantity and stability.The expiration date was determined via the accelerated stability test(temperature at 40 C ±2 C,relative humidity at 75%±5%)and long-term stability test(closed condition,temperature at 25 ? ±2?,relative humidity at 60%± 10%).Result:1.The primary extraction solvent was detennined based on the extracted syringa vulgaris by comparing water,50%,60%,70%,80%and 95%of ethanol as the solvent.The extracted syringa vulgaris was 32.47 ?g/mL,32.63 ?g/mL,32.30 ?g/mL,32.57 ?g/mL,32.07 ?g/mL and 32.87 ?g/mL,respectively.Since no significant difference was observed(P>0.05),water was chosen as the primary extraction solvent.The best primary extraction protocol using the water as solvent was developed based on the conversion rate of the syringa vulgarns.The orthogonal design was used to find the best parameters for the water-extraction process.Finally,the parameters were determined as 10 volumes of water,one hour per extraction,three extractions total.2.The ethanol precipitation was applied as the next refine-extraction step.The refine-extraction protocol using ethanol was developed based on the loss-rate of the syringa vulgaris and less ethanol usage.The final parameters were determined as following.The best concentration before ethanol precipitation was 1.5 g drug/mL.The ratio of water-extracted drug:ethanol was 1:1(v/v).The ethanol precipitation time was 12 hours.The final content of syringing vulgarns was 17.75 mg/mL and the loss-rate of syringing vulgaris was 14.50%.3.The ethanol-precipitated drug was further concentrated based on the concentration of syringing vulgaris and the density of the thick-paste drug.The best concentration was determined as a relative density of 1.15.4.The best drying protocol were determined based on the content of syringing vulgaris,the observed properties and moisture in the dried product.The final process parameters for the decompression drying are-0.05?-0.1 MPa,60?-70?.Under these conditions,the drug is crisp,easy to crush,less than 6.0%of water and with higher syringing vulgaris content(greater than 0.90mg/g).5.The formulation process was performed as below.The dried drug was grounded and filtered through the 80-mesh screen.The anhydrous glucose was added and mixed well with the dried drug powder at2?3:1 ratio.6.The quality standard was established through observation with three different individual batches of the pilot samples.The powder color is observed as light yellow to brown.The content of Acanthopanax,Astragalus and angelica in the powder was identified using TLC.The detected color and position should be same with that of the control.The HPLC was used to detect the syringing vulgaris content as 0.240mg/g,0.243mg/g and 0.238mg/g for the three different individual batches,respectively.It was determined that not less than 0.2mg/g is required with the syringing vulgaris content.The loss-limit of water is not more than 6.0%.7.The final product was stable for 6 months under the accelerated stability test(temperature 40 ? ± 2 ?,relative humidity 75%± 5%)and for 12 months under long-term stability test(closed,temperature 25?± 2 ?,relative humidity 60%± 10%).Therefore we temporarily set up the stable time as 2 years.Conclusion:We have successfully developed the extraction protocol and established the quality standards of Cihuangzengdan Powder.The data built up the required basis for further pharmacology,toxicology and clinic investigation with this new veterinary drug.