This report aimed to formulate self-micro-emulsifying (SMEDDS) controlled-release pellets delivery system to improve aqueous solubility and in vivo availability of eugenol, a main constituent of clove oil with multiple pharmacological activities. The optimal formulation of eugenol-SMEDDS was eugenol: ethyl oleate: cremophor EL: 1, 2-propylene glycol at the ratio of 5:5:12:8. The SMEDDS were observed under transmission electron microscopy (TEM), and the size distribution was measured with dynamic laser light scatting (DLS). The particle size, index of dispersity (PDI), and zeta potential (Z-potential) were 68.8 ± 0.1 nm, 0.285 ± 0.031, and − 11.62 ± 0.63 mV, respectively. Eugenol-SMEDDS exhibited substantial increased in vitro dissolution compared with the free eugenol. The eugenol-SMEDDS sustained-release pellets (eugenol-SMEDDS-SR pellets) comprising of eugenol-SMEDDS, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and ethyl cellulose (EC) coats were obtained via extrusion spheronization technique. Consequently, the obtained pellets observed under scanning electron microscopy (SEM) showed spherical shape with smooth surface, desirable drug loading capacity (7.18 ± 0.17%), greater stability, and controlled release. Meanwhile, the oral test showed that bioavailability of eugenol in pellets was highly improved 23.6-fold to the free eugenol. Overall, these results suggested that the improvement of the oral bioavailability of eugenol-SMEDDS-SR could be due to the successful incorporation of the drug into SMEDDS.
eugenol SMEDDS sustained-release pellet drug release oral bioavailability
Self-microemulsifying drug delivery system
High-performance liquid chromatography
Caprylic capric triglyceride
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The authors thank the University Ethics Committee for the kind guidance in the animal experiments.
This work was supported by the National Natural Science Foundation of China (81273470, 81473172, and 81503025), National “Twelfth Five-Year” Plan for Science & Technology Support (Grant 2013BAD16B07-1), Special Funds for 333 and 331 projects (BRA2013198), Indus-try University-Research Institution Cooperation (JHB2012-37, GY2012049, GY2013055) in Jiangsu Province and Zhenjiang City, Program for Scientific Research Innovation Team in Colleges and Universities of Jiangsu Province, and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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