Design of alginate-based aerogel for nonsteroidal anti-inflammatory drugs controlled delivery systems using prilling and supercritical-assisted drying

摘要

In this study, a novel preparation method for alginate-based aerogels charged with nonsteroidal anti-inflammatory drugs (NSAIDs) was developed using prilling in combination with supercritical fluid technique. Nanoporous carriers were prepared by laminar jet breakup of drug/alginate solutions or suspensions followed by cross-linking in ethanol or aqueous CaCl2 solutions, water replacement, and supercritical-CO2-assisted drying. A substantial drug loss was observed for highly soluble ketoprofen lysinate, whereas encapsulation efficiency was satisfying for slightly soluble ketoprofen. The tandem technique successfully produced almost spherical aerogels (sphericity coefficient 0.97-0.99) in narrow size distribution with reduced particle shrinkage and smooth surface (surface roughness 1.10-1.13); the internal porous texture of the parent hydrogels was preserved and appeared as a network of nanopores with diameters around 200nm. Drug release profiles were monitored using a pH change method to evaluate the possible application of the aerogels as fast dissolving NSAIDs formulation. Aqueous cross-linking led to aerogels encapsulating ketoprofen in the amorphous form and with an enhanced burst effect in simulated gastric fluid (75% in 30min), whereas ethanol cross-linking produced aerogels embedding drug in crystal clusters with slower dissolution rate. The system appears an interesting potential carrier for the fast delivery of slightly soluble drugs in the upper gastrointestinal tract.