Preparation and optimization of altrenogest self-microemulsion drug delivery system
In order to improve the solubility and oral bioavailability of altrenogest in vivo,a self-microemulsion drug delivery system(ALT-SMEDDS)was developed and characterized.The study delved into the influencing factors and self-emulsifying mechanism of ALT-SMEDDS.Experimentation involved saturation solubility tests to discern the drug-carrying capacity of various excipients,while physical and chemical compatibility experiments were employed to ascertain the judicious compounding of these excipients.The formulation composition and the excipient dosage range of ALT-SMEDDS were systematically screened using pseudo ternary phase diagrams,and the effects of the ratio of oil phases and the mass ratio of emulsifiers to co-emulsifiers(Km)on the formation of self-microemulsions were also investigated.Further refinement of the formulation was achieved through the application of central composite design-response surface methodology(CCD-RSM).Through the regression model,and results of variance analysis,it was obtained that the self-emulsifying time was greatly affected by Km,which increased with the Km,while the average particle size was greatly affected by the oil phase,and which increased with the proportion of the oil phase.When the oil phase is ethyl oleate(22.0wt％),the surfactant was Tween80(54.2wt％)and the co-surfactant was Transcutol HP(23.8wt％),ALT-SMEDDS exhibited a clear and transparent appearance with excellent flowability.The self-emulsifying time of ALT-SMEDDS was 35.76±1.10 s.The droplets displayed a rounded and homogeneous structure,devoid of adhesion.The average particle size of ALT-SMEDDSD was 18.39±0.03 nm,the PDI was 0.083±0.090,and the Zeta potential was-1.12±0.12 mV,indicating stability within the range of 10～1000 fold dilution.ALT-SMEDDS showcased an impressive cumulative release of 91.41％at 48 h in vitro,signifying a substantial improvement compared to the original drug release of 32.42％.With its reliable prescription,high emulsification efficiency,uniform microemulsion particle size distribution,and overall stability,ALT-SMEDDS emerges as a promising candidate for enhancing the in vitro release of ALT.This sets a solid foundation for the prospective clinical application of ALT-SMEDDS in improving the therapeutic efficacy of ALT.
altrenogestself-microemulsion drug delivery systemcentral composite design-response surface methodologysurfactantpseudo-ternary phase diagram
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