Aqueous solubility study of salts of benzylamine derivatives and p-substituted benzoic acid derivatives using X-ray crystallographic analysis

TY - JOUR

T1 - Aqueous solubility study of salts of benzylamine derivatives and p-substituted benzoic acid derivatives using X-ray crystallographic analysis

AU - Parshad, Henrik

AU - Frydenvang, Karla Andrea

AU - Liljefors, Tommy

AU - Sorensen, Henning Osholm

AU - Larsen, Claus

PY - 2004

Y1 - 2004

N2 - Twenty two p-substituted benzoic acid derivates were used to prepare salts of N-methylbenzylamine (II) and N,N-dimethylbenzylamine (III), respectively. Only five salts of (II) and two salts of (III) were obtained in a crystalline state. The solubility of these salts was orders of magnitude higher than those reported for the corresponding salts of benzylamine (I). Thermal analysis indicated that the increased solubility was caused by reduced crystal lattice energy, which was most likely due to the reduced number of strong hydrogen bonds of the salt of (II) and (III). X-ray crystallographic analysis of p-hydroxybenzoic acid salt of (I), (II) and (III) suggested that the reduced number of hydrogen bonds caused the apparent higher solubility. Further analyses of seven salts of (I) were performed. It was not possible to identify any relationship between the number of hydrogen bonds and the corresponding solubility of the salts.

AB - Twenty two p-substituted benzoic acid derivates were used to prepare salts of N-methylbenzylamine (II) and N,N-dimethylbenzylamine (III), respectively. Only five salts of (II) and two salts of (III) were obtained in a crystalline state. The solubility of these salts was orders of magnitude higher than those reported for the corresponding salts of benzylamine (I). Thermal analysis indicated that the increased solubility was caused by reduced crystal lattice energy, which was most likely due to the reduced number of strong hydrogen bonds of the salt of (II) and (III). X-ray crystallographic analysis of p-hydroxybenzoic acid salt of (I), (II) and (III) suggested that the reduced number of hydrogen bonds caused the apparent higher solubility. Further analyses of seven salts of (I) were performed. It was not possible to identify any relationship between the number of hydrogen bonds and the corresponding solubility of the salts.

KW - Benzoic Acids

KW - Benzylamines

KW - Chemistry, Physical

KW - Crystallography, X-Ray

KW - Hydrogen Bonding

KW - Molecular Conformation

KW - Physicochemical Phenomena

KW - Solubility

KW - Water

M3 - Journal article

C2 - 14698587

SN - 0378-5173

VL - 269

SP - 157

EP - 168

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1

ER -