### Abstract

The solubilities in water and 1-octanol of 22 nitrogen-bridgehead quinazolone derivatives were investigated. The data were determined with a conventional method, with the typical confidence intervals at 95% probability level about ±5% and the precision good enough to evaluate the influence of structural modifications and to compare data with the lipophilicity of molecules. Solubilities in water spanned five orders of magnitude depending on the substituents attached to the ring-system. The solubility in octanol was generally somewhat higher and the range was only three magnitudes. Aqueous solubilities were more sensitive to structural changes than those in octanol. Solubility ratios were computed and fitted to the predictive relationship with two independent variables proposed by Yalkowsky. The equation with solubility ratios gave better results than the one calculated with experimental log P (partition coefficient) values. That corresponds to the known difference of solubility ratios (log SR) and log P values, caused mainly by the mutual solubility of two phases in log P measurements. The solubility ratio and the partition coefficient have the same trend but the values differ significantly. Thus the partition coefficient and the solubility ratio are not recommended for estimation of aqueous solubility (log S(w)) data of these compounds.

Original language | English |
---|---|

Pages (from-to) | 233-242 |

Number of pages | 10 |

Journal | International Journal of Pharmaceutics |

Volume | 159 |

Issue number | 2 |

DOIs | |

Publication status | Published - Dec 15 1997 |

### Fingerprint

### Keywords

- Aqueous solubility
- Estimation of aqueous solubility
- Estimation of lipophilicity through solubility data
- Estimation of log P
- Nitrogen-bridgehead compounds
- Solubility in octanol
- Solubility ratio

### ASJC Scopus subject areas

- Pharmaceutical Science

### Cite this

**Determination of solubilities in water and 1-octanol of nitrogen- bridgehead heterocyclic compounds.** / Józan, Miklós; Takács-Novák, K.

Research output: Contribution to journal › Article

*International Journal of Pharmaceutics*, vol. 159, no. 2, pp. 233-242. https://doi.org/10.1016/S0378-5173(97)00292-5

}

TY - JOUR

T1 - Determination of solubilities in water and 1-octanol of nitrogen- bridgehead heterocyclic compounds

AU - Józan, Miklós

AU - Takács-Novák, K.

PY - 1997/12/15

Y1 - 1997/12/15

N2 - The solubilities in water and 1-octanol of 22 nitrogen-bridgehead quinazolone derivatives were investigated. The data were determined with a conventional method, with the typical confidence intervals at 95% probability level about ±5% and the precision good enough to evaluate the influence of structural modifications and to compare data with the lipophilicity of molecules. Solubilities in water spanned five orders of magnitude depending on the substituents attached to the ring-system. The solubility in octanol was generally somewhat higher and the range was only three magnitudes. Aqueous solubilities were more sensitive to structural changes than those in octanol. Solubility ratios were computed and fitted to the predictive relationship with two independent variables proposed by Yalkowsky. The equation with solubility ratios gave better results than the one calculated with experimental log P (partition coefficient) values. That corresponds to the known difference of solubility ratios (log SR) and log P values, caused mainly by the mutual solubility of two phases in log P measurements. The solubility ratio and the partition coefficient have the same trend but the values differ significantly. Thus the partition coefficient and the solubility ratio are not recommended for estimation of aqueous solubility (log S(w)) data of these compounds.

AB - The solubilities in water and 1-octanol of 22 nitrogen-bridgehead quinazolone derivatives were investigated. The data were determined with a conventional method, with the typical confidence intervals at 95% probability level about ±5% and the precision good enough to evaluate the influence of structural modifications and to compare data with the lipophilicity of molecules. Solubilities in water spanned five orders of magnitude depending on the substituents attached to the ring-system. The solubility in octanol was generally somewhat higher and the range was only three magnitudes. Aqueous solubilities were more sensitive to structural changes than those in octanol. Solubility ratios were computed and fitted to the predictive relationship with two independent variables proposed by Yalkowsky. The equation with solubility ratios gave better results than the one calculated with experimental log P (partition coefficient) values. That corresponds to the known difference of solubility ratios (log SR) and log P values, caused mainly by the mutual solubility of two phases in log P measurements. The solubility ratio and the partition coefficient have the same trend but the values differ significantly. Thus the partition coefficient and the solubility ratio are not recommended for estimation of aqueous solubility (log S(w)) data of these compounds.

KW - Aqueous solubility

KW - Estimation of aqueous solubility

KW - Estimation of lipophilicity through solubility data

KW - Estimation of log P

KW - Nitrogen-bridgehead compounds

KW - Solubility in octanol

KW - Solubility ratio

UR - http://www.scopus.com/inward/record.url?scp=0344835855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344835855&partnerID=8YFLogxK

U2 - 10.1016/S0378-5173(97)00292-5

DO - 10.1016/S0378-5173(97)00292-5

M3 - Article

AN - SCOPUS:0344835855

VL - 159

SP - 233

EP - 242

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 2

ER -