Correlation of aqueous solubility of salts of benzylamine with experimentally and theoretically derived parameters. A multivariate data analysis approach

TY - JOUR

T1 - Correlation of aqueous solubility of salts of benzylamine with experimentally and theoretically derived parameters. A multivariate data analysis approach

AU - Parshad, Henrik

AU - Frydenvang, Karla Andrea

AU - Liljefors, Tommy

AU - Larsen, Claus Selch

PY - 2002

Y1 - 2002

N2 - Twenty two salts of benzylamine and p-substituted benzoic acids were prepared and characterized. The p-substituent was varied with regard to electronic, hydrophobic, and steric effects as well as hydrogen bonding potential. A multivariate data analysis was used to describe the relationship between the aqueous solubility of the salts and experimentally determined physicochemical parameters and theoretically derived molecular descriptors. The model, based on all descriptors, gave R(2)=0.86 and Q(2)=0.72. The most significant descriptors exhibiting VIP (variance of importance) values above 1.0 were intrinsic dissolution rate, intrinsic solubility of the unionized acids (S(0)), Hansch's hydrophobic parameter, Charton's steric parameter and molecular weight (MW). Statistically good models for predicting solubility of a selected test set were obtained by using simple models consisting of a few descriptors only: (i) Charton, Hansch and MW (R(2)=0.73; Q(2)=0.70), and (ii) Charton and S(0) (R(2)=0.74; Q(2)=0.72).

AB - Twenty two salts of benzylamine and p-substituted benzoic acids were prepared and characterized. The p-substituent was varied with regard to electronic, hydrophobic, and steric effects as well as hydrogen bonding potential. A multivariate data analysis was used to describe the relationship between the aqueous solubility of the salts and experimentally determined physicochemical parameters and theoretically derived molecular descriptors. The model, based on all descriptors, gave R(2)=0.86 and Q(2)=0.72. The most significant descriptors exhibiting VIP (variance of importance) values above 1.0 were intrinsic dissolution rate, intrinsic solubility of the unionized acids (S(0)), Hansch's hydrophobic parameter, Charton's steric parameter and molecular weight (MW). Statistically good models for predicting solubility of a selected test set were obtained by using simple models consisting of a few descriptors only: (i) Charton, Hansch and MW (R(2)=0.73; Q(2)=0.70), and (ii) Charton and S(0) (R(2)=0.74; Q(2)=0.72).

KW - Benzylamines

KW - Least-Squares Analysis

KW - Models, Chemical

KW - Multivariate Analysis

KW - Salts

KW - Solubility

KW - Thermodynamics

KW - Water

M3 - Journal article

C2 - 11955817

SN - 0378-5173

VL - 237

SP - 193

EP - 207

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -