Preparation And Vitro Dissolution Of Tamoxifen Citrate Tablets

Tamoxifen citrate tablets are non-steroidal and anti-estrogen drugs,developed by Astra Zeneca Pharmaceutical Co.,Ltd.which is the first choice for clinical treatment of breast cancer.The original research products are not imported or commercialized in China,the current Chinese listed tamoxifen citrate tablets are generic drugs.In order to improve the clinical safety and effectiveness of the domestic generic drugs,to ensure that the bioavailability is consistent with the original development agent.The research work on the preparation and in vitro dissolution experiments of tamoxifen citrate tablets was carried out.Tamoxifen citrate was synthesized with qualified purity,and its crystal form,melting point,particle size and related substances meet the 2015“Chinese Pharmacopoeia”quality standards.By analyzing the prescription composition of the original developer,not only the use of each excipient was inferred,but also the binder concentration,filler ratio,disintegrant dosage and lubricant dosage in the prescription were examined.The optimal formulation was determined by screening:the binder was 10%aqueous gelatin solution,the disintegrant was croscarmellose sodium（3%）,the filler was lactose hydrate and starch（weight ratio 3:1,82%）,the lubricant was magnesium starate（1.5%）,hypromellose,polyethylene glycol 300 and titanium dioxide are coating materials.By examining the process conditions such as granulation mode,granulation mesh number,mixing time,moisture content and drying temperature,the optimal preparation process was selected as the mixing time of 15 min,the wet granulation was passed through 20 mesh,the drying temperature was 60^oC and controls the moisture content to 3～5%,then adjusts the material filling and pressure to obtain 180 mg round tablets,and final tablets were obtained after a furth coating.In this paper,several batches of tamoxifen citrate tablets（1000 tablets/batch）were prepared under the optimal prescription and process conditions.The angle of repose,crystal form,sheet weight difference,hardness,friability,disintegration degree,content and dissolution were also measured.The results of the measurement showed that the quality of the homemade tamoxifen citrate tablets was in accordance with the provisions of the 2015“Chinese Pharmacopoeia”.In order to further evaluate the difference between the homemade tablets and the original developer,this paper also established the method for determining the vitro dissolution profiles of tamoxifen citrate tablets.Finally,p H 1.2,p H 3.0,p H 6.8 and the aqueous solution were selected as the dissolution medium（900 m L）by investigating absorption wavelength.The p H-solubility,dissolution apparatus,volume of dissolution medium,sampling time,rotation speed,instrument precision,filter adsorption,linear range,recovery rate,reference substance and the stability of the solution were tested.Slurry method was used under the rotation speed of 50 r·min^-1,after filtered through a 0.45μm filter,the absorbance was measured by ultraviolet-visible spectrophotometry at 275 nm,and the dissolution at each time point was calculated by the reference method.Meanwhile,the similar factor method（f₂method）was used to evaluate the dissolution behavior of the original tamoxifen citrate tablets,domestic generic drugs and homemade tablets in the four dissolution media.The experimental results showed that the f₂value of the tamoxifen citrate tablets（prepared by the method of this present invention）and the original preparation is greater than 50,and the homemade tablets have similarities with the original preparations.Finally,this paper made a preliminary investigation on the mixing and granulation process parameters of the small test magnification,prepared and tested the quality of three batches of tamoxifen citrate tablets.The result of small test magnification meets the quality requirements of the 2015“Chinese Pharmacopoeia”.