Supercritical impregnation of chitosan sponges with 17β-estradiol

Abstract

Chitosan sponges with open porous structures have great potential as drug delivery matrices for constructing transdermal patches. Supercritical solvent impregnation (SSI) is an advantageous green technique for the inclusion of hydrophobic drugs into porous matrices. In this work SSI of chitosan sponges with 17β-estradiol (E2) using a supercritical scCO2 /ethanol medium under static conditions was investigated. In the SSI study, the influence of such operating parameters as temperature (35 and 65 °C), pressure (15–120 MPa, which corresponds to density of CO2 815–1142 kg m-3.), and a molar fraction of the drug (from 2.3 ×10-3 mol% to 8.9 ×10-3 mol% from CO2 amount) in the reactor on the loading capacity and the efficiency of the uptake was evaluated. It was revealed that hormone loading increased linearly with the initial concentration of E2 and CO2 density in the reactor. The developed processing parameters for SSI made it possible to vary the loading of E2 into the chitosan sponges in a wide range from a few to hundreds of µg per mg of the matrix, which corresponds to the adequate doses range of the hormone used in transdermal delivery. The successful inclusion of E2 into the polymer matrices was proven by UV spectroscopy, powder X-ray diffraction, fluorescence microscopy, and scanning electron microscopy. It was found that SSI method provides a strong micronization and a uniform distribution of E2 crystallites in the sponge volume, which may positively affect the bioavailability of the drug.