[Construction and application of composite drug delivery system combining liquid self-microemulsifying and solid...

The low water solubility of tanshinone components(TSC) limits their quality and functionality. This study innovatively constructed a composite drug-loading system of TSC self-microemulsifying dispersed micro-tablets by integrating the solubilization advantages of self-microemulsions with the stability characteristics of solid preparations. First, based on solubility tests, compatibility experiments, and pseudo-ternary phase diagram analysis, a ternary self-microemulsion system composed of ethyl oleate, polyoxyethylene castor oil, and absolute ethanol was established, and the self-microemulsion formation process was optimized using a central composite design-response surface methodology. Under the optimal self-microemulsifying conditions, the equilibrium solubility of TSC increased to(58.65 ± 0.18) mg·mL~(-1), exhibiting excellent centrifugation and dilution stability. In vitro drug release studies demonstrated that the TSC self-microemulsifying system significantly improved drug release, achieving complete release within 48 h in HCl medium. Subsequently, the matrix formulation of the dispersed micro-tablets was determined through single-factor screening. The resulting micro-tablets exhibited good mechanical properties and rapid dispersion characteristics, while particle size distribution after dissolution and transmission electron microscopy images confirmed effective maintenance of the self-microemulsion structure. Fourier transform near-infrared spectroscopy, X-ray diffraction, and simultaneous thermal analysis indicated that TSC was successfully encapsulated within the self-microemulsifying dispersed micro-tablets, while also highlighting the need for temperature protection during production. This study successfully established a novel "liquid self-microemulsifying-solid dispersed micro-tablet" composite drug-loading system, providing a new approach for improving the bioaccessibility of TSC.