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
Temperature dependencies of saturated vapor pressure for the monoclinic modification of paracetamol (acetaminophen), acetanilide, and phenacetin (acetophenetidin) were measured and thermodynamic functions of sublimation calculated (paracetamol: ΔGsub298 = 60.0 kJ/mol; ΔHsub298 = 117.9 ± 0.7 kJ/mol;...
Saved in:
Published in | Journal of pharmaceutical sciences Vol. 95; no. 10; pp. 2158 - 2169 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English Russian |
Published |
Hoboken
Elsevier Inc
01.10.2006
Wiley Subscription Services, Inc., A Wiley Company Wiley American Pharmaceutical Association |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Temperature dependencies of saturated vapor pressure for the monoclinic modification of paracetamol (acetaminophen), acetanilide, and phenacetin (acetophenetidin) were measured and thermodynamic functions of sublimation calculated (paracetamol: ΔGsub298 = 60.0 kJ/mol; ΔHsub298 = 117.9 ± 0.7 kJ/mol; ΔSsub298 = 190 ± 2 J/mol · K; acetanilide: ΔGsub298 = 40.5 kJ/mol; ΔHsub298 = 99.8 ± 0.8 kJ/mol; ΔSsub298 = 197 ± 2 J/mol · K; phenacetin: ΔGsub298 = 52.3 kJ/mol; ΔHsub298 = 121.8 ± 0.7 kJ/mol; ΔSsub298 = 226 ± 2 J/mol · K). Analysis of packing energies based on geometry optimization of molecules in the crystal lattices using diffraction data and the program Dmol3 was carried out. Parameters analyzed were: (a) energetic contribution of van der Waals forces and hydrogen bonding to the total packing energy; (b) contributions of fragments of the molecules to the packing energy. The fraction of hydrogen bond energy in the packing energy increases as: phenacetin (17.5%) < acetanilide (20.4%) < paracetamol (34.0%). Enthalpies of evaporation were estimated from enthalpies of sublimation and fusion. Activity coefficients of the drugs in n‐octanol were calculated from cryoscopic data and by estimation of dilution enthalpy obtained from solubility and calorimetric experiments (for infinite dissolution). Solubility temperature dependencies in n‐octanol and n‐hexane were measured. The thermodynamic functions of solubility and solvation processes were deduced. Specific and nonspecific solvation terms were distinguished using the transfer from the “inert” n‐hexane to the other solvents. The transfer of the molecules from water to n‐octanol is enthalpy driven for paracetamol; for acetanilide and phenacetin, entropy driven. © 2006 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2158–2169, 2006 |
---|---|
Bibliography: | ArticleID:JPS20674 istex:E7089B7B7F358DD4B9A94086A91B5872C4E9AAC4 ark:/67375/WNG-7R4MKNG5-Q ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3549 1520-6017 |
DOI: | 10.1002/jps.20674 |