Self-emulsifying Dropping Pills Loaded with Pueraria Total Flavones
|Keywords||Pueraria total flavones self-emulsifying dropping pills release characteristics invitro bioavailability|
Pueraria total flavones are an active ingredient extracted from the traditionalChinese herb Pueraria, which has been widely used to treat cardiovascular andcerebrovascular diseases. Due to its poor water and oil solubility and absorption afteroral, its clinical therapeutic effect has been limited. The SMEDDS is used to a vehicleto increase water solubility and the absorption of insoluble drugs, then increasingbioavailability and avoid the fluctuation of serum concentration. However, liquidSMEDDS has carrying disadvantageous and poor stability. Therefore, pueraria totalflavones are developed to self-microemulsion dropping pills, which would solve theproblem.To prepare an optimized SMEDDS, the solubility of various oils and surfactantswere investigated, Ternary phase diagrams and pseudo-ternary phase diagrams wereconstructed and in vitro properties of formulations were evaluated. The optimizedSMEDDS was pueraria total flavones (15.0%), Crodamol GTCC (17.0%), Maisine35-1(17.0%), Cremophor RH40(30.6%),1,2-Propanediol (20.4%). Theself-emulsifying time of SMEDDS was less than2minutes; the droplet sizedistribution and Zeta-potential of the resultant microemulsion were19.23nm and-4.11mV. The optimized formulation was used for be quite stable during six monthsof study period.The optimized self-emulsifying dropping pills loaded with pueraria total flavoneswere prepared by single factor test and orthogonal design, in which SMEDDS:PEG6000=1:3.5. The optimized condition of moulding technics of dropping pillswere temperature of drugs (80℃), the speed of dropping (50drops per minute), thedistance of dropping (10cm) and the temperature of condensing agent (2~10℃). Theself-emulsifying time was below7minutes, and the mean droplet size andZeta-potential of the resultant emulsion were34.32nm and-6.33mV respectively.The in vitro release experment dissolution behavior of pueraria total flavones fromSMEDDS exhibited the independence of the kind of medium, and the cumulativerelease of pueraria total flavones was95%, dissolving faster. The optimizedformulation was used for be quite stable during six months of study period.The plasma concentration of self-emulsifying dropping pills loaded with puerariatotal flavones and Yu feng ning xin dropping pills in Wistar rats was determined byHPLC, and the pharmacokinetics were processed by DAS2.1software. The resultsindicated that Tmaxwas later and Cmaxwas higher than Yu feng ning xin dropping pills.The oral bioavailability of PTF-SMEDDS was improved significantly. The relativebioavailability of PTF-SMEDDS was (236±40)%, compared with commercial dropping pills.