Preparation And Bioequivalence Evaluation Of Paroxetine Hydrochloride Enteric-Coated Sustained-Release Tablets

Objective:To develop a preparation of Paroxetine Hydrochloride Enteric-Coated Sustained Release tablets,through in vitro dissolution behavior and in vivo bioequivalence tests,finally obtained a generic preparation with the same quality as PAXIL CR in efficacy and safety.Methods:Through the project research,combined with the reverse engineering of the original research to determine the paroxetine extend-release tablets of the initial prescription,process;Study the paroxetine hydrochloride,study its crystal form,solubility etc,to ensure that the raw material drug standards can be carried out the next step of the preparation study;Analyze the key quality attributes of the original product,such as the release curve,etc.,as the main evaluation index during the development of the self-made products;By screening the prescription,examining the durability of the process,determine preliminary prescriptions for small-scale production;The pilot-scale equipment which is consistent with the principle of the small scale production equipment is used to carry out the pilot-scale research,to verify the range of the technological parameters,to continuously produce 3 batches of samples,and to ensure that the quality is is consistent with the original product;The bioequivalence test was carried out with one batch of pilot-scale samples and two batches of original research product by single dose,self-control and triple cross test design.Result:Purchased raw materials do not need further treatment,can directly meet the needs of the preparation;The best formulation prescription:Drug-containing layer:paroxetine hydrochloride 28.51 mg,lactose monohydrate 40mg,HPMC K10038.5mg,HPMC K4M 27.5mg,magnesium stearate lmg,appropriate amount of 8%PVP K30 aqueous solution;Barrier layer:lactose monohydrate 20mg,HPMC E340mg,glyceryl behenate 15mg,red ferric oxide 0.1 mg,magnesium stearate lmg,appropriate amount of 8%PVP K30 aqueous solution.Small scale-up of the process:Raw material sieved through 80 mesh sieve,when mixed the drug-containing layer 10min、15min,the contents equal to 99.6%、99.8%,RSD value is 1.09%、0.55%.When granulating,the stirring speed is 600 rpm and the cutting speed is 1200 rpm,and to grain 1min,over 20 mesh nylon mesh,dry to moisture ≤3.0%;The total mixed average content of 97.6%,RSD value of 1.21%.compression process control pressure:80-130N,the difference between the weight of ±4%,Enteric coating weight gain control in 11.0%to 13.0%,film coating weight gain control in 2%to 4%.Pilot enlargement:self-made preparations of the indicators meet the requirements.In vitro evaluation:the self-made products release curve similar to the original research.The BE test results show that the self-made products and the reference preparations are bioequivalent.Conclusion:The formulation of the self-made preparation is reasonable;the production process has good reproducibility and stability;the quality of the produced self-made product is controllable and meets the quality standards of paroxetine hydrochloride enteric sustained-release tablets;the appearance of the self-made product is the same as the original product,in vitro dissolution characteristics are consistent;self-produced and original research products are bioequivalent.