Study On The Preparation Process Of Simvastatin Mixed Micellar Tablets

Objective: Use simvastatin as a model drug to prepare mixed micelles to solve the shortcomings of low solubility and rapid elimination,optimize the preparation process of simvastatin mixed micelles,verify the characterization,and study its stability;The preparation process of its tablets was studied.Methods: High performance liquid chromatography was used to establish an in vitro analysis method for simvastatin;single micelles and mixed micelles were compared with Encapsulation efficiency(EE%),Drug-loading rate(DL%),particle size and other indicators;simvastatin mixed micelles were prepared by thin film hydration method,Taking the EE%,DL% and Leak rate(LR%)of the micelles as the inspection indicators,the single factor method and the star point design-effect surface method are used to optimize the optimal preparation process and the best prescription of the mixed micelles;through transmission electron microscopy,particle size,Differential scanning calorimetry and infrared spectroscopy are used to characterize mixed micelles;the critical micelle concentration of mixed micelles is studied by iodine-ultraviolet spectrophotometry;the particle size,PDI and Zeta potential of mixed micelles are analyzed Stability and redispersibility are studied;the solubility of micelles is measured by the measurement of saturated solubility,and the cumulative release is used to verify that the micelles have a sustained release ability;then they are prepared into tablets,and the appearance,hardness and The friability and other indicators were investigated to optimize the optimal preparation process of tablets;the cumulative release was used as the indicator to investigate the p H stability and release properties of the mixed micelles.Result: The in vitro analysis of simvastatin by high performance liquid chromatography is stable and feasible;simvastatin mixed micelles are better than single micelles in terms of EE%,DL% and stability;simvastatin mixed micelles are hydrated by film Preparation method,the best prescription is Pluronics P123-F127 as the mixed carrier,absolute ethanol as the organic solvent,the rotary steaming temperature is set at 55℃,the hydration temperature is set at 45℃,the hydration time is set at 1h,and the verification test results are average EE % Is 95.31%,the average DL% is 5.37%,and the average LR% is 11.54%;the result of the freeze-drying process is that the freeze-drying protection agent is not added,the pre-freezing time is15 h,and the freeze-drying time is 30h;the transmission electron microscope results show that the mixed glue The beam is regular round,the drug is coated in the core of the micelle,the average particle size is 19.26 nm,the PDI is 0.094,and the zeta potential is-11.3m V.The results of differential scanning calorimetry and infrared spectrum scanning show that the characteristic peaks of the drug substance disappear.The critical micelle concentration of the mixed micelle is 0.0058mg/100ml;the solubility is increased by about 2000 times;the stability is good after three months at room temperature,and the redispersibility of the lyophilized powder is good;the mixed micelle is stable in acid,at p H 7.0 The buffer solution has obvious slow-release effect;the mixed micelles are prepared into tablets,the filler is determined to be microcrystalline cellulose,the glidant is magnesium stearate,and the amount of glidant is 3%.The verification test shows that the The process is stable and feasible.Conclusion: The preparation process of simvastatin mixed micellar tablets is simple and stable,and is suitable for large-scale industrial production.Effectively solve the shortcomings of simvastatin low solubility and fast release.