Functionalization of Silica Surfaces: Influence in Naproxen Molecular Mobility and Release Profile

This work aimed to improve aqueous drug solubility by amorphization upon loading in silica porous matrixes and stabilize it in the amorphous form. Naproxen was chosen as the target material, a practically insoluble pharmaceutical drug, with anti-pyretic and anti-inflammatory properties. To evaluate the influence of guest-host interactions in the drug delivery, two silica matrixes were synthesized differing in their surface composition: unmodified MCM-41 mainly with surface silanol groups and MCM-41_Func caped with methyl groups. The surface area modification with methyl groups was confirmed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and nuclear magnetic resonance (NMR). Textural analysis showed narrow pore diameter distributions centered at 3.0 and 2.9 nm, respectively. To evaluate the guest’s physical state, different techniques were used as: differential scanning calorimetry (DSC), dielectric relaxation spectroscopy (DRS) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. These analyses showed that naproxen was successful incorporated in the both silica. The naproxen’s amorphization was confirmed by the DSC detection of the glass transition, located in between ~0ºC and 22ºC. However, crystallization and melting are always observed, nonetheless in low extent (~6 % of crystallization degree). The mobility of the amorphous pharmaceutical drug incorporated inside these silica pores, was probed by DRS, allowing estimating a dielectric glass transition temperature in good agreement with the calorimetric one and revealing a higher mobility for the hydrated unmodified composite. It was shown that this mobility enhancement controls the drug delivery, monitored by ultraviolet spectroscopy, which revealed to be faster in the unmodified matrix. The studied composites show promising behavior as controlled drug delivery systems