| Total flavonoids from leaves of Diospyros kaki,which widely used as herbal remedy for centuries,has comprehensive pharmacological activity and especially play a significant role in protecting the cardiovascular system.However,with poor solubility in water as well as slow dissolution rate in vivo,its oral absorption is limited,leading to clinical application and formulation development in trouble.In order to improve the solubility of total flavonoids in persimmon leaves and improve its bioavailability,this paper combines self-microemulsion and liquisolid technique to develop an new preparation of solid self-microemulsion--liquid-solid compressed tablets of self-microemulsion containing total flavonoids from leaves of Diospyros kaki.Firstly,to provide the basis for subsequent formulation research and quality control,this paper inspected the following items: the establishment of content determination method and dissolution method,and study of the basic physical and chemical properties of drugs.Having examined solubility of drug in self-microemulsion accessories and checked the compatibility of the accessories to select suitable accessories.The result was: MCT as oil,RH-40 as emulsifier,THP as auxiliary emulsifier,which holds the properties of well solubility and emulsification.And then having determined the scope of each component in prescription by drawing the pseudo ternary phase diagram of forming microemulsion.With ratio of MCT,RH40 and THP as independent variables,as well particle size,polydispersity index and the drug loading as the evaluation indexes,having optimized the formulation by preliminary experiment and simplex lattice methodology.Optimized formulation for self-microemulsion was 10%MCT,30%RH-40,60%THP.On the basis of the self-microemulsion prescription,the model of liquidsolid compression was used as the convergence point,and the liquidsolid technique was used to study the preparation of the total flavonoids from persimmon leaves.Themaximum retention potential(Φ)for solid material adsorbing from the self-microemulsion(MCT-RH40-THP)and disintegration time as well as dissolution of tablets were investigated to select liquidsolid compression materials.The result was:MCC PH-101 as carrier material,Sylysia as coating material,PVPP as disintegrating agent.With the ratio of drug to excipient,R value and dosage of disintegrating agent as independent variables,as well dissolution rate as the evaluation indexes,optimizing the formulation by Box-Benhnken design response surface methodology.Optimized prescription was as follow: the ratio of drug to excipient was 0.2,R value was 16,and dosage of disintegrating agent was 8.0%.Study on the properties of microemulsion solid compression system containing total flavonoids from persimmon leaves were reviewed,including liquid self-microemulsion system,self-microemulsion solid compression powder system and self-microemulsion solid compression tablet system.It revealed that self-microemulsion were O / W emulsion with low viscosity,small particle size of(33.1 ±0.51)nm,narrow polydispersity index of(0.165±0.01)and zeta potential of(-17.21 ± 0.04)mV;The powder had good fluidity,better filling and well wettability;The tablet maintained the characteristics of liquid self-microemulsion emulsification with small particle size of(49.5±0.63)nm,narrow polydispersity index of(0.169±0.08)and zeta potential of(-11.50±0.06)mV,which was not significantly different compared with liquid self-microemulsion system.Simultaneously,it had good content uniformity,and its’ dissolution was higher than municipal tablet and API.Finally,the properties,identification,and preliminary stability of liquid-solid compressed tablets of self-microemulsion containing total flavonoids from leaves of Diospyros kaki were investigated to study the quality of the preparation.The result was that the preparation of the preparation complied with the requirements and its’ stability was well. |
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