Research On Application In Preparation Of Breviscapine Solid Dispersion By A Novel Carrier Soluplus~?

Objective: This study aims to apply a novel carrier Soluplus~? to preparation of breviscapine solid dispersion by solvent evaporation method and hot-melt extrusion technology,select the optimal formulation and process,enhance the in vitro dissolution of breviscapine,a active but poorly water-soluble ingredient of traditional Chinese medicine(TCM).By comparing the pros and cons of the two kinds of preparation process,we are going to optimize the best formulation and process that will be scaled up for production,and finally to solve the problem of low oral bioavailability of breviscapine.Methods: On one hand,Soluplus~? was applied to the preparation of breviscapine solid dispersion by solvent evaporation method,and preliminary screening of eight kinds of carrier materials was conducted with evaluation index of dissolution.The formulation and preparation process were optimized by carrier proportion enhancement,carrier combination,crystal inhibitors addition and particle size reduction.On the other hand,Soluplus~? was applied to preparation of breviscapine solid dispersion by hot-melt extrusion,compared with three other kinds of carriers.By carrier proportion enhancement and plasticizer addition,the formulation was optimized,and double screw rotation speed and feeding speed were investigated that are two kinds of key process parameters of hot-melt extrusion process,and the comparison and evaluation were conducted of both preparations of solid dispersion.The formulation by solvent evaporation method was selected and characterized by means of scanning electron microscopy(SEM),differential scanning calorimetry(DSC),powder X-ray diffraction(PXRD),Fourier transform infrared spectrometry(FT-IR).The stability of the formulation was investigated with appearance and content as indexes.On this basis,the solid dispersion tablet was prepared and its formulation was preliminarily investigated.Results: In terms of preparation of breviscapine solid dispersion by solvent evaporation method,when the 1:9 ratio of breviscapine and Soluplus~?,the particle size was controlled through 80 mesh sieve,the solubilization effect of breviscapine solid dispersion is most obvious,whose cumulative dissolution percentage is 93.4% which is 6.6 times as much as API’s;while in the application of hot-melt extrusion technology,Soluplus~? has better solubilization effect than the other three carriers.As the carrier proportion increased from 1:9 to 1:17,cumulative dissolution percentage decreased first and then increased;that was enhanced with Kolliphor ELP as plasticizer.Double screw rotation speed had no effect on of cumulative dissolution percentage,and feeding speed had a great effect.DSC and PXRD results showed that the breviscapine has highly dispersed in Soluplus~? in amorphous state while FT-IR result showed that scutellarin and Soluplus~? were associated in the possible form of intermolecular hydrogen bonds.The formulation by solvent evaporation method has a good stability and was not easily aging.The cumulative dissolution percentage of tablets prepared with the tablet weight of 600 mg 90.7% which was increased from 74.2% of the commercially available tablets by using crospovirone as the disintegrant,monohydrate lactose and microcrystalline cellulose(1: 1)as the filler.Conclusions: The novel carrier Soluplus~? can obviously enhance the in vitro dissolution of breviscapine by preparation of solid dispersion through solvent evaporation method and hot-melt extrusion which is better than the other carriers.The stability of solid dispersion is good.Scutellarin was highly dispersed in Soluplus~? in amorphous state and both were associated in the possible form of intermolecular hydrogen bonds.From the point of current results,solvent method is more suitable for the preparation of breviscapine solid dispersions while hot-melt extrusion needs to be further explored in its formulation and process.