title: Energetic aspects of diclofenac acid in crystal modifications and in solutions--mechanism of solvation, partitioning and distribution.
abstract: Temperature dependency of saturated vapor pressure and heat capacity for the diclofenac acid (Form II) were measured and thermodynamic functions of sublimation calculated (DeltaG(sub)(298) = 49.3 kJ x mol(-1); DeltaH(sub)(298) = 115.6 +/- 1.3 kJ x mol(-1); DeltaS(sub)(298) = 222 +/- 4 J x mol(-1) x K(-1)). Crystal polymorphic Forms I (P2(1)/c) and II (C2/c) of diclofenac acid have been prepared and characterized by X-ray diffraction experiments. The difference between crystal lattice energies of the two forms were obtained by solution calorimetry: DeltaDeltaH(sol)(I --> II) = 1.6 +/- 0.4 kJ x mol(-1). Temperature dependencies of the solubility in buffers with pH 2.0 and 7.4, n-octanol and n-hexane were measured. The thermodynamic functions of solubility, solvation, and transfer processes were deduced. Specific and non-specific solvation terms were distinguished using the transfer from the "inert" n-hexane to the other solvents. The transfer of diclofenac acid molecules from the buffers to n-octanol (partitioning and distribution) is an entropy driven process.
authors: Institute of Pharmacy, University of Tromsø, Breivika, N-9037 Tromsø, Norway.
authors: German L
authors: GL
authors: Perlovich
authors: Artem O
authors: AO
authors: Surov
authors: Lars Kr
authors: LK
authors: Hansen
authors: Annette
authors: A
authors: Bauer-Brandl
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004008:Diclofenac / Q000737:chemistry*; D006586:Hexanes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D011312:Pressure; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002021:Buffers; D006586:Hexanes; D012996:Solutions; D012997:Solvents; D004008:Diclofenac; C026385:n-hexane; D020003:1-Octanol