Sulfonic Acid Derivative-Modified SBA-15, PHTS and MCM-41 Mesoporous Silicas as Carriers for a New Antiplatelet Drug: Ticagrelor Adsorption and Release Studies

Three mesoporous, siliceous materials, i.e., SBA-15 (Santa Barbara Amorphous), PHTS (Plugged Hexagonal Templated Silica) and MCM-41 (Mobil Composition of Matter), functionalized with a sulfonic acid derivative, were successfully prepared and applied as the carriers for the poorly water-soluble drug, ticagrelor. The siliceous carriers were characterized using nitrogen sorption analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM) and elemental analysis. The adsorption studies were conducted in acetonitrile. At the highest equilibrium concentrations, the amount of ticagrelor Q(e) that adsorbed onto the examined silicas was in the range of 83 to 220 mg/g, increasing in the following order: PHTS-(CH(2))(3)-SO(3)H < SBA-15-(CH(2))(3)-SO(3)H < MCM-41-(CH(2))(3)-SO(3)H. The equilibrium adsorption data were analyzed using the Freundlich, Jovanovich, Langmuir, Temkin, Dubinin-Radushkevich, Dubinin-Astakhov and Redlich-Peterson models. In order to find the best-fit isotherm for each model, a nonlinear fitting analysis was carried out. Based on the minimized values of the ARE function, the fit of the isotherms to the experimental points for ticagrelor adsorption onto the modified silicas can be ordered as follows: SBA-15-(CH(2))(3)-SO(3)H (Redlich-Peterson > Dubinin-Astakhov > Temkin), PHTS-(CH(2))(3)-SO(3)H (Redlich-Peterson > Temkin > Dubinin-Astakhov), MCM-41-(CH(2))(3)-SO(3)H (Redlich-Peterson > Dubinin-Astakhov > Langmuir). The values of adsorption energy (above 8 kJ/mol) indicate the chemical nature of ticagrelor adsorption onto propyl-sulfonic acid-modified silicas. The results of release studies indicated that at pH 4.5, modified SBA-15 and MCM-41 carriers accelerate the drug dissolution process, compared to the dissolution rate of free crystalline ticagrelor. Intriguingly, modified PHTS silica provides prolonged drug release kinetics compared to other siliceous adsorbents and to the dissolution rate of crystalline ticagrelor. A Weibull release model was employed to describe the release profiles of ticagrelor from the prepared carriers. The time necessary to dissolve 50% and 90% of ticagrelor from mesoporous adsorbents at pH 4.5 increased in the following order: SBA-15-(CH(2))(3)-SO(3)H < MCM-41-(CH(2))(3)-SO(3)H < PHTS-(CH(2))(3)-SO(3)H.