Effect of DMSO on micellization, gelation and drug release profile of Poloxamer 407

The application of many recently developed or approved drugs and pharmaceuticals is seriously hampered by their low solubility in aqueous media. Hence, numerous promising pharmaceutical delivery systems (including novel “smart” systems based on poloxamer gels, which have highly advantageous thermo-reversible characteristics and low toxicity) cannot solubilize required doses of various drugs without additives such as co-solvents or salts. Therefore, we have studied the effects of dimethyl sulphoxide (DMSO) – a commonly used co-solvent during drug development stages – on the micellization, gelation and dissolution properties of aqueous poloxamer solutions. Differential scanning calorimetry and tube inversion experiments clearly showed that DMSO induces reductions in the critical micellization and gelation temperatures of poloxamer systems. In addition, high resolution solid state 1H Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses provided indications of the specific chemical groups in the poloxamer affected by DMSO, and the molecular mechanism involved. The presence of DMSO accelerated dissolution of the pure gel in water and the release of a hydrophobic drug (flufenamic acid) from poloxamer gel, while it reduced the release of a hydrophilic drug (metoprolol tartrate).