Chemical-physical study of ibuprofen incorporated into unmodified and modified mesoporous silicas: from matrix synthesis to drug release

This work aims to rationalize the release profile of a poorly water-soluble drug loaded in mesoporous silica matrices, in terms of guest-host interactions. The incorporation of pharmaceutical drugs in a matrix was extensively studied as a strategy to stabilize the amorphous form and simultaneously enhance the solubility of currently commercial drugs. Ibuprofen (Ibu) containing antipyretic, analgesic and anti-inflammatory properties was loaded with two mesoporous inorganic silicas MCM-41, with and without modification by silylation (MCM-41sil). Nitrogen adsorption-desorption analysis exhibited a narrow pore size distribution characteristic of this type of silica. The success of the silica surface modification was confirmed by infrared spectroscopy (ATR-FTIR), solid state nuclear magnetic resonance (ssNMR) and nitrogen porosimetry analysis. The drug loading was performed by capillarity under vacuum and the resulting composites were spectroscopic analyzed by thermogravimetric (TGA), differential scanning calorimetry (DSC), ATR-FTIR and ssNMR. The presence of a glass transition characteristic of ibuprofen amorphization, shifted to higher temperatures, and the absence of the melting peak (Tm = 77 ºC) by DSC together with the TGA data showing a two-step decomposition profile confirm the presence of two different molecular populations, one more bulk-like and another one in a closer interaction with the pore walls. This effect is most evident in ibuprofen loaded in MCM-41sil due to stronger host interactions with the surface of the mesoporous host. The drug release studies in the composites were performed in phosphate buffer solution, pH 6.8, 37 ℃ and 100 rpm, to simulate the intestinal fluid and analyzed at 222 nm with UV-VIS spectroscopy and the results adjusted using different kinetic models. Both composites were shown to be efficient as ibuprofen release systems, with the ibuprofen loaded in MCM-41sil presented a lower release rate, which corroborates the results obtained by DSC and TGA showing a greater interaction of the drug with the matrix