Diclofenac, a non steroidal anti-inflammatory drug, is poorly soluble in water and exists as dimers in the solid state, bound together hydrogen bondings, involving the carboxylic groups, which are destroyed by the formation of a salt. Salts of alkaline metals are hydrate: their solubility in water is not so high as that of other sodium or potassium NSAID salts, and their behavior in water solution suggests self-aggregation. Salts formed with hydroxy aliphatic amines, despite the hydrophilic contribution of increasing number of hydroxy groups, have limited solubility in water, which is inversely related to the melting point of the salt. The nature of this behavior is explained by the solid state structure, since these salts exist as ion-pairs, where hydroxy groups of each cation are strictly hydrogen bonded with the corresponding diclofenac anion: this structure in most cases originates high melting point and reduce solubility. Finally the diclofenac/N-pyrrolidine-ethanol salt forms hydrate polymorphs and has a complex behavior in the slid state, as a function of RU, temperature and pressure and also in its aqueous solutions. The formation of polymorphs is suspected also in the case of other three diclofenac salts, by the profile of DSC thermograms, at high temperature scanning.
Adamo Fini, Giuseppe Fazio, Laura Benetti (2005). SOLUBILITY AND SOLID STATE STRUCTURE OF SOME DICLOFENAC SALTS. NICE : PharmSciFair.
SOLUBILITY AND SOLID STATE STRUCTURE OF SOME DICLOFENAC SALTS
FINI, ADAMO;
2005
Abstract
Diclofenac, a non steroidal anti-inflammatory drug, is poorly soluble in water and exists as dimers in the solid state, bound together hydrogen bondings, involving the carboxylic groups, which are destroyed by the formation of a salt. Salts of alkaline metals are hydrate: their solubility in water is not so high as that of other sodium or potassium NSAID salts, and their behavior in water solution suggests self-aggregation. Salts formed with hydroxy aliphatic amines, despite the hydrophilic contribution of increasing number of hydroxy groups, have limited solubility in water, which is inversely related to the melting point of the salt. The nature of this behavior is explained by the solid state structure, since these salts exist as ion-pairs, where hydroxy groups of each cation are strictly hydrogen bonded with the corresponding diclofenac anion: this structure in most cases originates high melting point and reduce solubility. Finally the diclofenac/N-pyrrolidine-ethanol salt forms hydrate polymorphs and has a complex behavior in the slid state, as a function of RU, temperature and pressure and also in its aqueous solutions. The formation of polymorphs is suspected also in the case of other three diclofenac salts, by the profile of DSC thermograms, at high temperature scanning.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.