Ordered Mesoporous Silica for Drug Delivery in Topical Applications

The aim of this PhD work was to develop and characterize all physicochemical aspects of this new CRT for CTZ and AKS using OMS until the introduction onto the market. The first part comprehends the characterization of different OMS synthesized and commercially available; the study of different incorporation techniques based on hydrophilicity/hydrophobicity of API; the characterization of the new impregnated OMS. Consequently, the work is oriented on the interaction details of API on silica surfaces. A closer look is given to the big questions of OMS-drug phenomena: mobility, solubility, bioavailability, etc. Therefore, all the scCO2 incorporation parameters have been studied, highlighting the differences between OMS and the spatial assembly of drug inside the mesoporous channels. Thus, the patented CRT has been developed for AKS describing all the main aspect of the innovative semisolid formulation. In-vitro and ex-vivo release test has been produced and characterized, revealing the functionality of the OMS reservoir effect. Finally, the same DDS have been developed for CTZ. Both the DDS have been compared with commercially available creams

A green organic-solvent-free route to prepare nanostructured zinc oxide carriers of clotrimazole for pharmaceutical applications

In the context of proposing cleaner production strategies for the pharmaceutical industry, an organicsolvent-free route to prepare nanostructured zinc oxide (NsZnO) reservoirs of clotrimazole (CTZ) was studied. Two different NsZnO materials were synthesized, selecting wet chemical approaches without any organic solvents: chemical bath deposition and a soft-template sol-gel method. Both materials showed a pure crystalline wurzite structure with two different morphologies: aggregates of nanosheets or interconnected nanoparticles. For the former material the specific surface area and the pore volume reached the values of 66 m2/g and 0,230 cm3/g, respectively, which were higher than those of the latter (19 m2/g and 0,050 cm3/g). For the first time, the loading of CTZ in a ZnO carrier was performed using supercritical CO2 as a solvent. The NsZnO materials were characterized, before and after the drug loading, by FESEM, EDS, XRD, nitrogen adsorption isotherms, TGA, DSC. CTZ was dispersed in the NsZnO carrier in amorphous form, with a maximum loading of 17% w/w. The decrease of specific surface area and pore volume upon drug loading for both samples is ascribed to the adsorption of CTZ molecules on the surface of the NsZnO materials. This confirms the feasibility of using the NsZnO as a CTZ carrier. In vitro drug-release was investigated and revealed that the NsZnO carrier can deliver CTZ with a faster release of a larger drug amount when compared to the solid crystalline drug. The novel clean preparation route of a ZnO carrier for CTZ delivery herein presented is easily adabtable to batch small-scale pharmaceutical industrial process

Simulation and Experiment Reveal a Complex Scenario for the Adsorption of an Antifungal Drug in Ordered Mesoporous Silica

Ordered mesoporous silicas have been widely investigated as drug carriers in several fields, from tissue engineering to cancer therapy. The knowledge of the specific interactions between the surface of mesoporous silicas and drugs is necessary to guide development of new and improved drug delivery systems. However, such knowledge is still scarce, due to the arduous interpretation of experimental results. In this work, we characterize the incorporation of clotrimazole, a common antifungal drug, inside ordered mesoporous silica by means of a joint computational and experimental approach. Experimentally the drug was loaded through supercritical CO₂ and its adsorption investigated through infrared spectroscopy, N₂ adsorption isotherms, and thermogravimetric analysis. Modeling involved static and dynamic Density Functional Theory simulations of clotrimazole adsorbed on realistic models of amorphous silica surfaces. A good agreement between the computational and the experimental results was obtained, concerning the energies of adsorption, the infrared spectra, and the distribution of drug inside the mesopores. However, a complete interpretation of the experimental results was possible only when simultaneously considering all the complex aspects of the drug–silica interaction. Indeed, the combination of both approaches allowed us to describe the drug–silica interface as a mix of multiple interaction configurations, based on a subtle balance of hydrogen bonding and dispersion interactions. Furthermore, at high drug loading, clotrimazole molecules are statistically distributed on the pore walls, forming an adsorbed molecular layer. Finally, notwithstanding the stable interactions, the drug still exhibits a significant mobility at room temperature, moving on a complex potential energy surface, as revealed by molecular dynamics simulations