The thermal, physical, and morphological properties of diphenhydraminium ibuprofenate ([DIP][IBU]) adsorbed onto mesoporous silica (SiO-60 Å and SiO-90 Å) from solution were determined. The thermal, physical, and morphological properties of [DIP][IBU] supported on silica were determined. The adsorption of [DIP][IBU] on the pores and surface of silica was proven by N adsorption/desorption isotherms. Additionally, release profiles were determined for all systems, and the antinociceptive activity of neat [DIP][IBU] and [DIP][IBU] supported on silica were determined. The interaction of [DIP][IBU] and silica was dependent on pore size, with the formation of a [DIP][IBU] monolayer on SiO-60 and a multilayer on SiO-90. The release profile was sustained and slow and dependent on the pore size of the silica, in which the smaller the pore size, the faster the release. The nociceptive evaluation showed that [DIP][IBU] presents a greater (99.21 ± 0.85%) antinociceptive effect than the ibuprofen (46 ± 4.3%). Additionally, [DIP][IBU] on SiO-60 (90 ± 5.8%) had a greater antinociceptive effect than on SiO-90 (73 ± 13.2%), which indicates that in vivo tests are in accordance with the in vitro experiments.
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