title: Interactions of ibuprofen with cationic polysaccharides in aqueous dispersions and hydrogels. Rheological and diffusional implications.
abstract: Non-steroidal antiinflammatory drugs, such as ibuprofen, are amphiphilic substances capable of self-association in aqueous solutions and able to be sorbed onto polymers through hydrophobic and electrostatic bonds. The aim of this work was to analyze the association processes of sodium ibuprofen with cationic celluloses (Celquat H-100 (PQ-4) and SC-230 M (PQ-10)) and cationic guar gums (Ecopol 261-S and 14-S) and their repercussions on the properties of the aqueous dispersions and cross-linked hydrogels. The interaction process was studied in aqueous dispersions through transmittance, surface tension, fluorescence, conductivity, viscosity and oscillatory rheometry measurements. Below cmc, the drug molecules weakly interact with the polymers through hydrophobic and ionic interactions. Around the cmc (4%), a notable decrease in the viscosity, and storage and loss moduli of the dispersions (even precipitation in PQ-10 systems) was observed. An additional increase in drug concentration induced the dispersions to recover their initial properties. Since ibuprofen/polymer cationic groups ratio were in all cases above 1, these observations indicate that drug self-association induces the polymer to coil around the micelles and, as the number of micelles increases (more drug concentration) the polymer chains interact with more of them, uncoiling again to some extent. Polymer (1%) dispersions containing 6% ibuprofen showed drug diffusion coefficients much lower than in water. When a surfactant, sodium dodecylsulfate, was added to these systems the diffusion coefficients decreased even more, suggesting the formation of new associative structures. Chemically cross-linked hydrogels made of these cationic polysaccharides absorb considerable amounts of ibuprofen (up to 15 g/g) and showed a pH-dependent release process. At acidic pH, drug-polymer affinity is maintained, preventing drug release. In contrast, at pH 8 the interactions are broken and the release process is sustained for more than 4h. In summary, ibuprofen interactions with cationic polysaccharides strongly determine the performance of their aqueous dispersions and hydrogels.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela 15782, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Rodríguez
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
mesh_terms: D002240:Carbohydrate Sequence; D002482:Cellulose; D003432:Cross-Linking Reagents; D004058:Diffusion; D004553:Electric Conductivity; D005685:Galactans; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D007421:Intestine, Small / Q000378:metabolism; D008351:Mannans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D053149:Plant Gums; D011134:Polysaccharides / Q000737:chemistry*; D012212:Rheology; D012967:Sodium Dodecyl Sulfate; D013056:Spectrophotometry, Ultraviolet; D013500:Surface Tension; D013501:Surface-Active Agents; D013535:Suspensions
chemical_list: D003432:Cross-Linking Reagents; D005685:Galactans; D020100:Hydrogels; D008351:Mannans; D053149:Plant Gums; D011134:Polysaccharides; D013501:Surface-Active Agents; D013535:Suspensions; D012967:Sodium Dodecyl Sulfate; D002482:Cellulose; C007894:guar gum; D007052:Ibuprofen