Towards an understanding of the molecular mechanism of solvation of drug molecules: A thermodynamic approach by crystal lattice energy, sublimation, and solubility exemplified by paracetamol, acetanilide, and phenacetin

Perlovich, German L.; Volkova, Тatyana V.; Bauer‐Brandl, Annette

doi:10.1002/jps.20674

Cited by 77 publications

(105 citation statements)

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“…The present work is a continuation of previous studies on thermodynamics of solvation of drug molecules (1)(2)(3)(4)(5)(6). Here, 2-acetaminophen and 3-acetaminophen molecules ( Fig.…”

Section: Introductionmentioning

confidence: 57%

Influence of Position and Size of Substituents on the Mechanism of Partitioning: A Thermodynamic Study on Acetaminophens, Hydroxybenzoic Acids, and Parabens

et al. 2008

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Abstract. The objective of the present investigation was to study the influence of size, nature, and topology of substituents on the thermodynamic characteristics of sublimation, fusion, solubility, solvation, and partitioning processes of some drug and druglike molecules. Thermodynamic functions of sublimation process 2-acetaminophen and 3-acetaminophen were obtained on the basis of temperature dependencies of vapor pressure by the transpiration method. Thermodynamic characteristics of solubility processes in water, n-octanol, and n-hexane were calculated from the temperature dependencies of solubility using the solubility saturation method. For evaluation of fusion parameters, differential scanning calorimetry was used. A new approach to distinguishing specific and nonspecific energetic terms in the crystal lattice was developed. Specific and nonspecific solvation terms were distinguished using the transfer from the "inert" n-hexane to the other solvents. For the acetaminophen compounds and for some related drug molecules, the correlation between melting points and a parameter describing the ratio between specific and nonspecific interaction in the crystal lattices was obtained. A diagram enabling analysis of the mechanism of the partitioning process was applied. It was found that for isomers of benzoic acids and for acetaminophens, the position of substituents affects the mechanism of the partitioning process but not the extent of partitioning ($G 0 tr values). In contrast to this, an increased size of substituents (parabens) leads to essential changes in $G 0 tr values, but the mechanism of the partitioning process stays the same.

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“…The present work is a continuation of previous studies on thermodynamics of solvation of drug molecules (1)(2)(3)(4)(5)(6). Here, 2-acetaminophen and 3-acetaminophen molecules ( Fig.…”

Section: Introductionmentioning

confidence: 57%

Influence of Position and Size of Substituents on the Mechanism of Partitioning: A Thermodynamic Study on Acetaminophens, Hydroxybenzoic Acids, and Parabens

et al. 2008

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“…All the experimental values of solubility, partitioning and sublimation for the evaluated drugs have been taken from the literature [2,[5][6][7]. The molecular structure and some physicochemical properties of the drugs are summarized in Table 1 [2,9].…”

Section: Resultsmentioning

confidence: 99%

“…The molecular structure and some physicochemical properties of the drugs are summarized in Table 1 [2,9]. The solubility in water and the ROH/W partitioning was determined at pH 7.4 (resembling the blood physiological value).…”

Section: Resultsmentioning

confidence: 99%

“…The values presented in Table 3, which are required for calculate the solvation quantities, were taken from Perlovich et al [2], and therefore, the function was calculated from values presented in Table 2.…”

Section: Thermodynamics Of Solution and Solvation At Saturationmentioning

confidence: 99%

“…As a contribution to systematization of physicochemical information about anti-inflammatory drugs' transfer properties, the main goal of this study was to analyze the solvation and dilution behavior of ACN, ACP, and PNC in the octanol/water (ROH/W) system by employing a thermodynamic approach based on solubility [5], partitioning [6,7] and sublimation processes [2]. From the obtained values of the corresponding thermodynamic quantities for drug's transfer processes, an interpretation based on solute-solvent and solvent-solvent interactions was developed.…”

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confidence: 99%

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Thermodynamic quantities of solvation and dilution for some acetanilide derivatives in octanol and water mutually saturateds

2008

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Modeling the solid–liquid equilibrium in pharmaceutical‐solvent mixtures: Systems with complex hydrogen bonding behavior

2009

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in Wiley InterScience (www.interscience.wiley.com).A methodology is suggested for modeling the phase equilibria of complex chemical mixtures with an equation of state (EoS) for the case where only limited experimental data exist. The complex hydrogen bonding behavior is explicitly accounted for and the corresponding parameters are adopted from simpler molecules of similar chemical structure and/or are fitted to Hansen's partial solubility parameters. The methodology is applied to modeling the solubility of three pharmaceuticals, namely acetanilide, phenacetin, and paracetamol, using the nonrandom hydrogen bonding (NRHB) EoS. In all cases, accurate correlations were obtained. The prediction ability of the approach was evaluated against predictions from the COSMO-RS model. A thorough discussion is made for the appropriate modeling of solid solubility considering the effect of the difference of the heat capacities of the solute in liquid and solid state, DCp 5 Cp l 2 Cp s , in the determination of solid chemical potential and, also, of the polymorphism of drugs.

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Towards an understanding of the molecular mechanism of solvation of drug molecules: A thermodynamic approach by crystal lattice energy, sublimation, and solubility exemplified by paracetamol, acetanilide, and phenacetin

Cited by 77 publications

References 31 publications

Influence of Position and Size of Substituents on the Mechanism of Partitioning: A Thermodynamic Study on Acetaminophens, Hydroxybenzoic Acids, and Parabens

Influence of Position and Size of Substituents on the Mechanism of Partitioning: A Thermodynamic Study on Acetaminophens, Hydroxybenzoic Acids, and Parabens

Thermodynamic quantities of solvation and dilution for some acetanilide derivatives in octanol and water mutually saturateds

Modeling the solid–liquid equilibrium in pharmaceutical‐solvent mixtures: Systems with complex hydrogen bonding behavior

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