Study Of Transdermal Drug Delivery System Of Sustained-release Coated Microspheres Containing Domperidone

Objective:Domperidone insoluble in water,and rapidly absorp after oral administration,15-30 min plasma concentration reached a peak.There is a "first effect" of liver metabolism and intestinal metabolism,and its oral bioavailability is low and so on.In this study,preparation of microspheres with domperidone increased the solubility and in vitro cumulative release.The microspheres were coated to a controlled release rate.Preparation of coated microspheres gels to drug transdermal administration and alter the problems associated with the traditional route of administration of domperidone.Methods:Microspheres were prepared by spray drying method.The optimal formulation was screened by solubility,particle size,drug loading,drug loading rate and cumulative release rate in vitro.Coated microspheres were prepared by emulsifying solvent evaporation method.The optimal formulation was screened by drug loading,drug loading rate,particle size,coating weight gain and in vitro cumulative release as the evaluation index.The optimal amount of accelerator and accelerator,the concentration of gel matrix and the drug loading of gel were screened by the cumulative dose of drug.Results:The optimal prescription of domperidone hyaluronic acid microspheres was HA 2 g,PEG 6000 1 g,DMP 0.5 g.The solubility was 121.81±2.63 μg·mL-1,the drug loading was 13.01 ±0.59%,the drug loading rate was 91.04±4.16%,the particle size was 1.39±0.10 μm,the cumulative release was 12.4.4± 1.45%.HA 1 g,PEG 6000 0.25 g,DMP 0.5 g,The solubility was 102.99±0.46 μg·mL-1,the drug loading was 27.96±1.17%,the drug loading rate was 97.86±4.10%,the particle size was 2.73±0.19μm,and the cumulative release at 12 h was 93.24±0.72%.The optimal coating microspheres were EC 0.1 g,microspheres 0.3 g,Span 80 1.5%.The drug loading was 7.92±0.05%,the drug loading rate was 136.04±0.88%,Coating weight gain was 39.08±0.40%,the particle size was 28.82±0.18 μm,and the cumulative release of 12 h was 95.34±4.04%.The optimal concentration of gel matrix in the percutaneous permeability test of coated microspheres was 1%,1%menthol,and the gel content was 1.5%.Pharmacokinetics showed that,The drug concentration of domperidone coated microspheres gels reached the maximum value at 4 of Cmax 0.49 ± 0.51μg·mL-1 h.t1/2 was 52.66±2.79 h and AUC was 14.53±4.75 μg·h·mL-1.The levels of Tmax,Cmax,t1/2 and AUC were significantly higher in the transdermal group than in the oral drug group and had some sustained-release effect,and improve the traditional DMP administration problems encountered.Conclusion:The preparation of microspheres improves the solubility and in vitro cumulative release of domperidone.Preparation of coated microspheres achieves the purpose of slow release.Preparation of coated microsphere gels to drug transdermal administration has altered the problems associated with the traditional route of administration of domperidone.