Correlation of aqueous solubility of salts of benzylamine with experimentally and theoretically derived parameters. A multivariate data analysis approach
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Correlation of aqueous solubility of salts of benzylamine with experimentally and theoretically derived parameters. A multivariate data analysis approach. / Parshad, Henrik; Frydenvang, Karla Andrea; Liljefors, Tommy; Larsen, Claus Selch.
In: International Journal of Pharmaceutics, Vol. 237, No. 1-2, 2002, p. 193-207.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 237
SP - 193
EP - 207
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -
ID: 40371843