Study Of Preparation Of Carvedilol Immediate-release And Sustained-release Preparations By Co-grinding Method

Carvedilol(CAR),a third-generation beta blocker,has many pharmacological effects.It is mainly used in the treatment of congestive heart failure,hypertension and angina pectoris.It belongs to the BCS II,which has low solubility restriction and low bioavailability,limiting its clinical application.Co-grinding technology promotes the dissolution of insoluble drugs by reducing the crystallinity,increasing the surface area,improving wettability and so on.This technique has the advantages of no organic solvent,simple operation and obvious effect.It has been extensively studied in recent years.CAR was used as the research object,and the co-grinding mixture was prepared by co-grinding technique in order to improve the water solubility,dissolution and the bioavailability of the drug.The details are as follows:a)Study of CAR before prescriptionAn in vitro analysis method for the determination of CAR was established.The results of the proposed method were feasible,reproducible,accurate and it could satisfy the requirements of the project.b)Preparation of CAR immediate-release co-grinding mixtureCAR-PVP K30 immediate-release co-grinding mixture was prepared by co-grinding method.The single factors such as milling time,milling speed and excipient ratio were investigated.The preparation conditions of CAR co-grinding mixture were studied by Central Composite Design Technology.The results showed that the dissolution rate and water solubility were greatly improved.c)Phase identification and characterization of immediate-release co-grinding mixtureThe results showed that the drug in the co-grinding mixture was mainly in the amorphous state.The stability of co-grinding mixture showed that the drug tended to absorb moisture easily.d)Preparation of CAR sustained-release co-grinding mixtureThe preparation conditions of CAR sustained-release co-grinding mixture were optimized by single factor investigation and Box-Behnken Design.The prepared co-grinding mixture exhibited a good sustained release effect.e)Phase identification and characterization of sustained-release co-grinding mixtureThe interations of CAR with EC N50 and PVP K30 were investigated by XRD,FTIR,PLM and SEM.On the other hand,the stability of controlled release co-grinding mixture was investigated.f)Preparation and stability study of CAR CapsulesThe moisture absorption and critical relative humidity of the contents of capsules were investigated.The release curve of sustained-release preparations showed that the release behavior was the double mechanism of drug diffusion and matrix dissolution.the stability of capsules showed that products was sensitive to high temperature and humidity.Therefore,the product should be sealed and stored in storage.The drug content nearly kept consistent with initial capsule after 3 months.