Research On Key Technologies Of Whole Process Controllable Powder Strengthening Mixing

The uniformity of raw material powder mixing and process reproducibility in the process of solid oral preparation are one of the technical prerequisites to ensure the consistent biological efficacy of solid oral preparation,therefore,the mixing uniformity and process reproducibility of continuous twin-screw mixer are the technical keys to evaluate the mixing performance.How to control the mixing uniformity and process reproducibility online and explain its regulation mechanism is a common technical problem to be solved urgently.In view of the common technical bottlenecks in the industry in the manufacture of solid oral preparations,which are difficult to control the mixing uniformity and process reproducibility of ultra-low component content and high cohesive raw material powder,the simulation method of powder mixing process in continuous twin-screw mixer was studied and established,the synergistic coupling evolution laws of ultra-low component content,cohesive viscosity characteristics—process parameters—structural characteristic parameters—powder mixing uniformity and process reproducibility were established by simulation,the cooperative coupling regulation mechanism is explained.The main conclusions are as follows:Under certain screw speed and mixing time,the influence of ultra-low component content and cohesive viscosity of raw material powder on the mixing performance of twin-screw powder mixer were simulated and studied,the relative standard deviation RSD of mixing uniformity and process reproducibility showed a negative correlation with the low component content of raw material powder formula,but a positive correlation with the cohesive viscous bulk energy density of raw material powder.When the mass fraction of low component in formula was reduced from 50%to 1.25%,the mixing uniformity RSD of low component content increased from 3.8%to 11%with an increase of 189.5%,and when the bulk energy density of raw material powder increases from 5000 J/m~3to 25000 J/m~3,the end-point mixing uniformity RSD increases from 2.71%to 6%with an increase of 121.4%.Its mixing uniformity and stability RSD exceed the technical requirements of FDA standard for mixing uniformity and stability RSD≤5%,which can be seen that the regulation of ultra-low component content and high cohesive viscosity raw material powder mixing uniformity is still a common technical bottleneck in the industry.Therefore,the key technology of enhanced mixing is innovatively proposed to realize the mixing uniformity and process reproducibility of raw material powder with ultra-low component content and high cohesive viscosity by increasing the screw speed of continuous twin-screw mixer,and the critical screw speeds to realize the enhanced mixing of raw material powder with different ultra-low component content and high cohesive viscosity were given.Aiming at the industry common technical bottleneck problem of the lack of real-time controllable release technology for the continuous twin-screw mixing uniformity and process reproducibility of ultra-low component content and high cohesive raw material powder,under the equivalent constraint control condition of mixing uniformity and process reproducibility of continuous twin-screw powder mixer with RSD=5%,the technical method of constructing the coupling evolution control curve of low component content of raw material powder,cohesive viscosity volume energy density of raw material powder and screw speed was creatively studied and put forward.Based on this research,the real-time release collaborative coupling control criterion and judgment curve were proposed in which the RSD of mixing uniformity and process reproducibility is controlled under 5%,the technical problem of real-time release collaborative coupling control of mixing uniformity and process reproducibility RSD≤5%of twin-screw powder mixer was solved.Under the conditions of different ultra-low component content and high cohesive viscosity,the synergistic coupling correlation control regression empirical model between RSD and screw speed was established,the real-time online model predictive control of mixing uniformity and process reproducibility in the cohesive or ultra-low content powder mixing process is realized by means of speed sensor,variable frequency drive motor and collaborative coupling correlation control regression model,which lay the foundation for solving the common technical bottleneck of the industry.