Transdermal Delivery of Estradiol Simultaneously Possessing Rapid Release and Sustained Release Effect

Dissolving microneedle (DMN) has been researched as a drug delivery technology that improves drug molecule transportation through the skin with little discomfort. However, the sluggish drug absorption, poor skin dissolution, and lengthy time lags of DMN have limited its potential uses. The aim of this study was to design a novel DMN system for the administration of the poorly water-soluble drug, estradiol (E2), with fast skin penetration and a stable release rate for a long time. DMN containing E2 emulsion (E2-EM-DMN) and traditional DMN (T-DMN) were prepared. Rat skin was used for penetration test and guinea pig skin was used for skin irritation experiment. The drug release profiles and stability properties of these two kinds of DMNs were also investigated. High performance liquid chromatography was employed to determine the E2 content in DMN. The E2 concentration in rat plasma was achieved by a newly developed liquid chromatography-mass spectrometry method that was fast, reproducible, and specific. The height of E2-EM-DMN and T-DMN was 600 μm. The drug loading of the E2-EM-DMN and T-DMN was 667.30 ± 7.21 μg/patch and 672.56 ± 6.98 μg/patch. E2-EM-DMN possessed enough mechanical strength to penetrate the skin and caused no irritation to the skin. E2-EM-DMN could release the drug more rapidly and more continuously than T-DMN. E2-EM-DMN had good pharmaceutical stability. In summary, the E2-EM-DMN showed reliable quality and superior release performance. Emulsion-embedded DMN is an ideal transdermal delivery system for drugs. Graphical Abstract