Tailoring the dissolution rate enhancement of aminoglutethimide by functionalization of MCM-41 silica: a hydrogen bonding propensity approach†
The adsorption and in vitro release properties of the poorly soluble cytostatic agent DL-aminoglutethimide (AGT) on pristine MCM-41, 3-aminopropyl and a novel N-propyl-2-sulfanylacetamide functionalized MCM-41 material were studied. The mesostructured supports and hybrid samples were characterized by small- and wide-angle X-ray diffraction, FT-IR spectroscopy, thermogravimetric and calorimetric analyses, SEM-EDX and N2 adsorption–desorption isotherms. The drug uptake was found to be strongly influenced by its ionization state and solution pH. Drug release experiments show a spectacular increase in the dissolution rate of the therapeutic agent for all hybrid samples, indicating that aminoglutethimide encapsulation into the mesopores of MCM-41-type supports is a viable strategy for dissolution rate enhancement. Using a knowledge-based logit hydrogen bonding propensity model to assess the relative strengths of drug–support supramolecular interactions, we have proposed that a Si–OH⋯Cl− AGT+ mechanism is responsible for the increased drug adsorption in acid media and release rate enhancement at physiological pH.