Incorporation of clotrimazole in Ordered Mesoporous Silica by supercritical CO2

Clotrimazole, a poorly water soluble antifungal active principle widely used in dermatology, was incorporated inside Ordered Mesoporous Silica (OMS) of the MSU-H type, using supercritical CO2 (scCO(2)) as solvent. The pristine OMS was characterized by a specific surface area of about 600 m(2)/g, a total specific pore volume of 0.900 cm(3)/g and an average pore size of 8.5 nm. The incorporation process was carried out in a high pressure stainless steel vessel at 25.0 MPa and 50.0 MPa, at 373 K. The time of incorporation process was varied from 6 to 18 h. The amount of incorporated clotrimazole was observed to increase with increasing incorporation time up to 12 h. Longer times (18 h) did not affect the incorporated amount. The maximum drug loading was 34% w/w, three times higher than that obtained by adsorption from ethanol solution (9.0% w/w). The clotrimazole-containing OMS was characterized by X-ray diffraction, field emission scanning electron microscopy, thermogravimetry, infrared spectroscopy and nitrogen adsorption. The clotrimazole resulted not crystalline and homogenously distributed inside the mesopores. A model of mesopores occupation by clotrimazole molecules in the form of a molecular layer is proposed. (C) 2014 Elsevier Inc. All rights reserved.