Preparation and Evaluation of Fenofibrate Self-microemulsifying Drug Delivery System
OBJECTIVE In order to improve the solubility and dissolution of the insoluble drug fenofibrate(FNB)optimize,the prescription of the self-microemulsifying drug delivery system(SMEDDS)was optimized and its quality was evaluated.METHODS The prescription composition and proportion range of SMEDDS were determined by the solubility experiment,compatibil-ity test and pseudoternary phase diagram.Star point design-response surface methodology was used to further optimize the formulation of fenofibrate self-microemulsifying drug delivery system(FNB-SMEDDS)by using solubility,average particle size and polydispersity index(PDI)as evaluation indicators.The physical and chemical properties,and preliminary stability of FNB-SMEDDS were evalua-ted.RESULTS The optimal prescription of FNB-SMEDDS was ethyl oleate(EO)22.86％as oil phase,polyoxyethylene(40)hydrogenated castor oil(cremophor RH40)51.07％as surfactant,diethylene glycol monoethyl ether(transcutol HP)26.07％as co-surfactant.The obtained FNB-SMEDDS was uniform and transparent.The FNB-SMEDDS was self-emulsified in water with average particle size of(39.29±0.45)nm,PDI of(0.11±0.01),Zeta potential of(-7.7±0.9)mV,drug loading rate of 15 mg·g-1,encapsulation rate of(95.11±0.26)％,and emulsification time of(56.03±1.65)s.Stability experiments showed that after being stored at room temperature in the dark for 30 days,there was no significant change in its index components and appearance properties,indicating good stability.Compared with FNB API,FNB-SMEDDS significantly improved the in vitro dissolution of FNB.The cumulative release rates in water,pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution for 120 min were(97.68±0.61)％,(92.23±4.07)％and(93.65±2.25)％,respectively.CONCLUSION FNB-SMEDDS has good appearance,high emulsification efficiency.It can significantly improve in vitro dissolution of the drug,and is expected to improve the in vivo bioavailability of FNB.
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