Preparation And In Vitro Release Of Venlafaxine Hydrochloride Sustained-release Tablets Based On Ion Exchange Resin

OBJECTIVE: This subject mainly studied the preparation and in vitro release of venlafaxine hydrochloride sustained-release tablets with ion exchange resin as a carrier.We firstly found out the suitable type of ion exchange resin and produced it into resinate.Then,we performed the confirmation experments and related research on prepared resinate.Finally,according to the in vitro dissolution data of different tablets,a prescription which can achieve a good sustain release effect was chosed and a release model fit was applied to the prescription.This project will promote the develepment of future research on ion exchange resins in pharmaceutical preparations.METHODS: By comparing the infrared spectrum of the resin,the venlafaxine hydrochloride drug substance,the physical mixture of the two,and the prepared compound of venlafaxine hydrochloride and the resin,it was confirmed whether the drug resin compound was prepared.The ion exchange resin required for the composite was screened by investigating the release rate of three resin composites of Amberlite IRP64,Amberlite IRP69 and Amberlite IRP88 and the drug loading rate of the three resins under the same preparation conditions.The preparation method was determined by single factor experiment to determine the conditions for preparing the drug resin composite,and the effects of temperature,rotation speed,ionic strength and particle type on the external release of the drug resin composite object were investigated.In this experiment,venlafaxine hydrochloride sustained-release tablets were prepared from two ideas.The first method did not use slow-release excipients,and investigated several commonly used binders.Investigated the release curves of different filler combinations and ratios to select the qualified prescriptions for verification.The second method used slow-release excipients to compare several commonly used HPMC models and proportions and fillers by single factor experiments.Proportionated the appropriate prescription and verifyed it.Finally compared the prescriptions selected by the two methods to determine the final prescription.The dissolution profile of the final prescription was fitted to the model by using Origin software.RESULTS: Infrared spectroscopy indicated that the drug resin compound was successfully prepared.Compared with Amberlite IRP64 and Amberlite IRP88 resin,IRP69 resin released the drug at a slower rate,and the drug download rate was higher under the conditions of the same preparation of the complex.Therefore,Amberlite IRP69 resin was chosed as the resin for following experiments.After studying the conditions for preparing a drug resin composite,the most suitable method for preparing the resinate was determined by the research: the temperature of the preparation solution was 25 ° C,the concentration ratio of the drug to the resin was 1:3,the preparation time was 2 h,and the preparation times were twice.The effects of temperature,rotation speed,ionic strength and particle type on the release of resinate were investigated.It was showned that under certain conditions,the higher the temperature,the faster the rotation speed,the faster the resinate releases the drug.The other conditions remained the same,the ionic strength and Ion species had no significant difference in the rate at which the drug resin compound released the drug.In the partial experiment of preparing venlafaxine hydrochloride sustained-release tablets,25% HPMC K100 LV was finally selected,and the prescription of lactose: MCC PH101=1:1 was used as the filler.There was no significant difference in the dissolution of the prescription in the three media of pH 6.8,pH 4.5 and pH 1.0.It can exhibit a good sustained release effect without release quickly phenomenon.The prescription can still achieve a good sustained release effect at high rotational speed,and no release quickly phenomenon.Therefore,the final prescription for this subject was selected here.The release curves of this prescription at pH 6.8 medium at different speeds were mathematically fitted.The dissolution profiles at 50 rpm,75 rpm and 100 rpm were all composite release models.Conclusion: The sustained release effect of the ion exchange resin itself is weak.In order to achieve a long sustained release effect,it needs to be combined with other slow release excipients.The release rate of the preparation can be adjusted according to the need of different viscosity type slow release excipients.This subject will provide a basis for the development of ion exchange resin in pharmacy,and provide some theoretical support for the application of Amberlite IRP69 resin.