Drug-Loaded Supramolecular Gels Prepared in a Microfluidic Platform: Distinctive Rheology and Delivery through Controlled Far-from-Equilibrium Mixing

Abstract

It is shown here that controlled mixing of a gelator, drug, solvent, and antisolvent in a microfluidic channel leads to faster setting gels and more robust materials with longer release profiles than the physical gels of the same composition obtained using random mixing in solution. The system is similar to a related gelator system we had studied previously, but we were unable to apply the same gelling procedure because of the instability of the colloid caused by the small structural modification (length of the alkyl chain in the bis-imidazolium head group). This situation holds true for the gels formed with varying compositions and under different conditions (gelator/drug ratio, solvent proportion, and flow rates), with the most significant differences being the improved gel rheology and slower drug release rates. Very importantly, the gels (based on a previously unexplored system) have a higher water content ratio (water/EtOH 4:1) than others in the family, making their medicinal application more attractive. The gels were characterized by a variety of microscopy techniques, X-ray diffraction and infrared spectroscopy, and rheology. Salts of the antiinflammatory drugs ibuprofen and indomethacin were successfully incorporated into the gels. The diffraction experiments indicate that these composite gels with relatively short alkyl chains in the gelator component contrast to previous systems, in that they exhibit structural order and the presence of crystalline areas of the drug molecule implying partial phase separation (even though these drug crystallites are not discernible by microscopy). Furthermore, the release study with the gel incorporating ibuprofenate showed promising results that indicate a possible drug delivery vehicle application for this and related systems.