The formation of pharmaceutical salts is widely recognized as a tool to improve the solubility in water of many acidic or basic drugs and modify their technological properties. This is also the case of diclofenac, an important member of non steroidal anti-inflammatory drug class, whose low solubility in water suggested formulations in the form of sodium and potassium salt, for oral delivery, and of diethylamine and N-pyrrolidine ethanol salts for topical applications. The interesting behavior of this last salt (DHEP), which forms polymorphs with different extent of hydration, and the easiness of dehydration of some alkaline diclofenac salts suggested the need of better examining the nature of the solid state of these salts, soon after their preparation or after equilibration with water in order to state the formation of hydrate and their stoichiometry. Diclofenac was studied with a variety of aliphatic amines with the aim to prepare salts with improved solubility, for a rapid availability. The crystal structure of many of these salts have been described and emerged that, beside the electrostatic interaction, typical of an ionic compound, a rather constant presence of hydrogen bonding between anion and cation contributes to a build a close contiguity between ions in the crystal lattice. This aspect, when present, could negatively affect the solubility in water, making useless the use of hydrophilic base to increase aqueous solubility of diclofenac salts. Diclofenac salts with aliphatic, cyclic or linear, hydrophilic or hydrophobic bases were examined by means of thermal analysis and displayed a wide range of behavior in the solid state, with the formation of hydrate and/or polimorphs and demonstrating a notable thermal instability. In particular, besides the case of DHEP, recently described, we observed bys HSM other polimorphism cases among these diclofenac salts and namely those prepared with the following bases: monoethanolamine, diethanolamine, N-methyl monoethanolamine and triethylamine.
Examples of polymorphism among diclofenac salts / A. Fini; G. Fazio; L. Benetti; V. Ghedini; S. DiGraci. - STAMPA. - (2006), pp. 172-172. (Intervento presentato al convegno XX Simposio ADRITELF tenutosi a Catania nel 4-7 ottobre 2006).
Examples of polymorphism among diclofenac salts
FINI, ADAMO;
2006
Abstract
The formation of pharmaceutical salts is widely recognized as a tool to improve the solubility in water of many acidic or basic drugs and modify their technological properties. This is also the case of diclofenac, an important member of non steroidal anti-inflammatory drug class, whose low solubility in water suggested formulations in the form of sodium and potassium salt, for oral delivery, and of diethylamine and N-pyrrolidine ethanol salts for topical applications. The interesting behavior of this last salt (DHEP), which forms polymorphs with different extent of hydration, and the easiness of dehydration of some alkaline diclofenac salts suggested the need of better examining the nature of the solid state of these salts, soon after their preparation or after equilibration with water in order to state the formation of hydrate and their stoichiometry. Diclofenac was studied with a variety of aliphatic amines with the aim to prepare salts with improved solubility, for a rapid availability. The crystal structure of many of these salts have been described and emerged that, beside the electrostatic interaction, typical of an ionic compound, a rather constant presence of hydrogen bonding between anion and cation contributes to a build a close contiguity between ions in the crystal lattice. This aspect, when present, could negatively affect the solubility in water, making useless the use of hydrophilic base to increase aqueous solubility of diclofenac salts. Diclofenac salts with aliphatic, cyclic or linear, hydrophilic or hydrophobic bases were examined by means of thermal analysis and displayed a wide range of behavior in the solid state, with the formation of hydrate and/or polimorphs and demonstrating a notable thermal instability. In particular, besides the case of DHEP, recently described, we observed bys HSM other polimorphism cases among these diclofenac salts and namely those prepared with the following bases: monoethanolamine, diethanolamine, N-methyl monoethanolamine and triethylamine.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
