Development Of Citalopram Hydrobromide Osmotic Pump Table

Part I Establishment of analysis method in vitro for Citalopram Hydrobromide tabletObjective:To establish an analysis method of Citalopram Hydrobromide tablet in vitro.Method:A series of analysis conditions in vitro,such as UV detection wavelength and dissolution medium,were determined by reviewing relevant literatures such as Chinese Pharmacopoeia(2015 edition)as well as examining the method specificity,linear range,and precision.Results:A method of releasing determination in vitro for Citalopram Hydrobromide was established.The UV spectrophotometric method with 238nm wavelength was used.The results showed the content was in compliance with the requirements.The release rate methodology study showed that the method for measuring the release of the product was good specificity,high precision and excellent accuracy,and the linearity,precision,and recovery rate of this method met the requirements.Part II Investigation of factors affecting coating process and preparation of Citalopram Hydrobromide osmotic pump tabletObjective:The coating film is very important for the quality of the osmotic pump table.The semi-permeable membrane material determines the permeability of the coating layer to water,thereby affecting the membrane osmotic pressure,which controls the effect of drug release.Therefore,this study investigated the factors of the coating process.Methods:The main cores of the Citalopram Hydrobromide tablet and the composition of the coating materials were basically determined by a series of pre-tests.The osmotic pump tablet was made under different coating conditions.By observing the status of the tablet and using the UV analysis method,the dissolution amount was measured and the dissolution curve was plotted,which obtained the optimum coating conditions through comparative analysis.Results:By investigating the factors of the coating process,the optimum coating conditions were achieved with the results of temperature of material25-28°C,inlet air 35°C,host speed of 9r/min,fan speed 1300r/min,and peristaltic pump speed rate 3.5r/min respectively.Conclusion:An excellent cellulose acetate coating should be colorlessly transparent.There were severe whitening of the outer layer of the coated tablets coupled with sticky-wall and sticky-film during the initial period of the test.The reasons contributing to that were over high coating temperature,quickly volatilized solvent,too fast peristaltic pump rotates and too much adhered-coating solution to the core.Therefore,lowering the coating temperature and slowing down the peristaltic pump speed could make good effect.Part III Preparation for Citalopram Hydrobromide osmotic pump tablets and optimization of design star-point formulationObjective:A series of single-factor studies and star-point design tests were performed to optimize the formulation of Citalopram Hydrobromide osmotic pump tablet through to make the drug release curve more stable.Method:The single-factor experiment method was used to determine the main factors affecting the drug release and the range of factors.The design formulations Were optimized by using the star point design-response surface optimization method,and the experimental results were brought into a mathematical model to obtain the best formulation.Finally,the fitting formulation was verified to determine whether it could improve the drug dissolution.Results:The amounts of PEO 5million and penetration enhancer,and the weight gain of the coating film were determined as the main factors affecting the drug release behavior after single-factor experiments.The optimized formulation from design star-point surface optimization method and Design-Expert 8.0 software made a near-zero release of the drug release curve and cumulative drug release percentage reached 93%after 12h.Conclusion:Due to its high precision and predictive value closed to the real value,the star-point design is a commonly used design method in recent years.The final optimization of formulation showed that the drug release rate was stable and the drug release curve was close to the zero-order rate equation(y=0.0812x+0.0702,R~2=0.9467).Part IV Pharmacokinetics of Citalopram Hydrobromide tablet in beagle dogsObjective:The Beagle dogs after fasting administration were treated with self-made preparations and commercial preparations respectively to determine the drug plasma concentration-time curve and to calculate the pharmacokinetic parameters and relative bioavailability with the design of two periodic double cycle cross test.Method:4 Beagle dogs were selected,male and female in half,about10-15kg.The animals were randomly divided into two groups,one group was treated with commercial Citalopram Hydrobromidetablet(Cipron)20 mg,and another group with a self-made osmotic pump table 20 mg for in vivo experiments.Results:In this part,HPLC method was used for the determination of plasma concentration of Citalopram Hydrobromide in Beagle dogs.The pharmacokinetic test in vivo results showed that the relative bioavailability of homemade osmotic pump controlled-release tablets to commercial tables was192.33%,and the drug was released smoothly.Conclusion:The results of pharmacokinetics test in beagle dogs showed that,compared with the commercial tables,the controlled-release tablets of homemade Citalopram Hydrobromide osmium pump had a lower peak concentration and a larger area under the plasma concentration-time curve,indicating that drug release can be more stable and plasma concentration be maintained for a long time.