| Duloxetine,a 5-HT and norepinephrine reuptake inhibitor,is widely used in the treatment of depression,developed by Lilly in the United States.The preparation is enteric-soluble,and the drug is located in the intestinal tract.It avoids the irritation to the stomach and makes the patient's compliance better.The purpose of this study is to imitate the original research drugs,explore the preparation process parameters,optimize the formulation,study the quality of products,and verify the analytical method of content and dissolution.The fluidization bed spray coating method was used in the sucrose starch blank blank pellet core(710~850 ?m)to take the medicine,the package isolation and the intestinal melting,and the finished product of the finished product of duloxetine hydrochloride was obtained.The effects of parameters such as fan frequency and inlet air temperature on the process were investigated.The effects of different adhesives and enteric materials on the release behavior in vitro were investigated.The better technical parameters and prescriptions are determined as follows.On the process: fan frequency is 22-25 HZ,inlet temperature is 58-63 ?,the material temperature is 40-43 degrees centigrade,atomization pressure is 1.0-1.2Mpa,peristaltic pump flow control in 2.0-4.0 RPM package;isolation process:Fan frequency is 25-28 HZ,inlet temperature is 58-63 ?,the material temperature is 40-43 degrees centigrade,atomization pressure is 1.2-1.6Mpa,peristaltic pump flow control in 2.0-6.0 rpm;enteric coated process: fan frequency 25-28 HZ,inlet temperature is 35-40 ?,the material temperature is 28-30 degrees centigrade,atomization pressure is 1.8-2.0 Mpa,peristaltic pump flow rate control in 9.0-12.0 rpm.Drug prescription: duloxetine hydrochloride 11.21 g,hydroxypropyl methyl cellulose HPMC E50 3.75 g sucrose,starch pellets(710-850 ?m 60.23 g),irrigation amount was110%;isolation layer prescription: talcum powder 12.46 g,hydroxypropyl methyl cellulose HPMC E50 3.75 g,the isolation layer thickness is 15.75%;enteric layer prescription:three citric acid ethyl ester 1.50 g,Eudragit Eudragit talcum powder 7.55 g,L30D-5550 g,64.73 g of distilled water,the enteric layer thickness is 15.25%.The dissolution behavior of Duloxetine Hydrochloride Enteric Capsule products in accordance with the 2015 edition of the Chinese pharmacopoeia standard was investigated.The dissolution conditions were as follows: rotating basket method,rotating speed100r/min,temperature setting(37±0.5)?.Take 10 mL of solution and add 10 mL ofmedium,UV absorbance value was measured,and cumulative dissolution rate was calculated,and the dissolution curve was drawn.The cumulative release amount of <10%pellets prepared by product testing at pH1.0 2 h in acidic medium,acid resistant;in other three media(pH6.8,pH6.0 and water)similarity factor release curve and curve of the goods were 62.57,81.37 and 73.87,in accordance with the relevant requirements of the similarities.In the matter study,enantiomer A=0.04%<0.5 %,while the remaining single miscellaneous peak area was between 0.01% and 0.06%,less than 0.1 %,and the total miscellaneous was between 0.15% and 0.16%,less than 1.5%.A methodological verification of liquid and ultraviolet dissolution of Duloxetine Hydrochloride Enteric Capsule was carried out.The results are as follows: the maximum absorption wavelength is 230 nm,the detection limit is 0.78 ng,the quantitative limit is2.17 ng,and the precision is good.Stripping method study of each verification results are in accordance with the regulations,suitable for self calibration of the dissolution determination of homemade duloxetine hydrochloride pellets.In the dissolution under ultraviolet radiation on the three batch of homemade duloxetine hydrochloride pellets dissolution were determined.The contents between 98%~102%,which accords with the requirements of dissolution standard. |
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