Preparation Of Duloxetine Hydrochloride Enteric Capsule

Objective: Duloxetine hydrochloride is a new type of depression in clinical,and it can be used in stress urinary incontinence and release the central nervous pain.The depression has made a serious harm for the society due to the high incidence,high recurrence and high suicide rate.In order to solve the safety and availability for the patients with depression during the dose,we developed duloxetine hydrochloride enteric capsule which is considered into the physical and chemical characters of duloxetine hydrochloride drug substance that is not stable in acid.Enteric-coated capsule is a multiple unit release system,which can effectively avoid the irritation of gastrointestinal tract occurred by the common dosage during local high concentration.Thus the adverse effect can be reduced.The modified dosage form can maintain the blood concentration within the therapeutic range to reduce the toxic and adverse effect occurred due to the variation of blood concentration.Based on the reasons explained above,the duloxetine hydrochloride is made of capsules which is filling with the enteric pills,which is not only the efficiency and safety can be enhanced,but also the availability for the patients is improved.There is a better clinical advantage.Methods:1 In this paper,to prepare duloxetine hydrochloride enteric capsuleas using duloxetine hydrochloride that is the API.According to the prescription of RLD and using sucrose blank pellets with yield as index,to determine the proportion of liquid coating layer,investigate the amount of different binder-HPMC.The performance of the FBD also has been studied and established the parameters of inlet air volume,spraying pressure,drying tempriture and spray speed.The effect of the coating weight to the dissolution has been studied.2 Research on quality control of duloxetine hydrochloride enteric capsules which is made inhouse.Established HPLC method for the determination of content and related compounds and carried out the methodological studies.According to USP 38 Appendix <711> to established HPLC method for the vitro releasing degree.The stirring rates in water were 100 rpm,the temperature was maintained at(37.5±0.5?).Used 900 ml water as the dissolution medium.The first 2h medium is 0.1mol/L HCl solutions(1000ml)and last hoursmedium is pH6.8 phosphate butter(1000ml),which can imitate the human situation.Samples were obtained at set time and calculated the drug concentration.During the stability test,the stress study,accelerated and long-term study have been done.For the stress study includes high temp.high humidity and light,sampled at day 0,day 5 and day 10.The test items for stability study include character,assay,related substances and dissolution.3 In vivo pharmacokinetic study,we used sample capsules made inhouse as the test drug and the drug made by Lily as reference to compelet the BE study.We carried out a randomized,single-dose,double-cycle,cross-dosing BE experimental design,and used the SAS software to analyze the main pharmacokinetic parameters to determine the pharmacokinetic behavior of the two drug consistency.Results:1 Through the study of formulation and process,the optimum formulation be determined:2 Confirmed test method for the determination of content and related compounds and carried out the methodological studies.Confirmed the pakage and storage conditions by stress testing and stability test,the result of the stability test show that the product quality is stable and controllable.3 Finally,It was proved that the drug is bioequivalence comparable with the commercial RLD by the pharmacokinetics.Conclusions: The duloxetine hydrochloride enteric capsule has a stable quality,which is manufactured with bedding coating process using FBD.The critical quality parameters include assay,related substances and release degree.The validated test methods are used for the test.The in vivo pharmacokinetic study,demonstrates that the product has a bioequivalence with the RLD got from the market.