Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid

Abstract

INTRODUCTIONUnderstanding the mechanism of passive transport is one of the most important issues in the design of new drugs. Since penetration of drugs through biological barriers is in many cases a major prerequisite for the biological effect, numerous attempts have been made to describe this process adequately. To cover the variability in biophysical characteristics of different membrane types, a set of 4 solvent systems has been used, sometimes called the "critical quartet" 1 : octanol-water (amphiphilic, aprotic solvent); propylenglycoldipelargonatwater (hydrogen bond acceptor); chloroform-water (hydrogen bond donor); and cyclohexane-water (purely hydrophobic).Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, ǻ , as well as the entropies of sublimation, ǻ , and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, ǻ , and the transfer Gibbs energy from water to octanol, ǻ . Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropycompensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed. ). This demonstrates once more that differently sized aggregates (subunits) take part in the elementary steps of diffusion, and that these subunits determine the diffusion mechanism (activation volume, activation thermodynamic parameters of the diffusion, and so on).

The SAMPL2 blind prediction challenge: introduction and overview

“…Also I have my own (rough) guesses as to K E values. The b-diketones (19)(20)(21) show some parallels with (24)(25)(26) and were chosen partly for this reason. Here (20, Z = CH 2 ) is pivotal: there is a possible ring size effect vs. (19, R = H); in (21) like (26) the OH tautomer is anti-aromatic; and some effect on K T is likely if Z = CH 2 is replaced by Z = O, S or NR, but its magnitude and direction are unknown.…”

“…(31) concerns the varying electron-deficiency of the 5-membered rings, which as it increases will, I believe, make the B-tautomer progressively more favoured. Finally, while the diazepine (32) exists overwhelmingly as the B-tautomer, this becomes antiaromatic in (33) and (perhaps less so) in (34), providing a further way, along with (21) and (26), of assessing a phenomenon which is known to be important but whose quantification has proved elusive.…”

Empirically Augmented Density Functional Theory for Predicting Lattice Energies of Aspirin, Acetaminophen Polymorphs, and Ibuprofen Homochiral and Racemic Crystals

“…(3), (4) and (5) have the smallest, the largest and intermediate absolute values. For comparison, the sublimation enthalpy of aspirin was experimentally determined as 109.7 kJ/mol at 298 K (45). Accordingly, the lattice energy can be approximated as j114.7 kJ/mol by Eq.…”

IUPAC-NIST Solubility Data Series. 102. Solubility of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) in Neat Organic Solvents and Organic Solvent Mixtures

“…Perlovich et al 102 determined the solubility of ibuprofen in eight 1-alkanols (methanol through 1-octanol) based on spectrophotometric measurements. Stovall et al 103 also used spectroscopic methods to measure the solubility of ibuprofen in six primary linear alcohols (methanol, ethanol, 1-propanol, 1-pentanol, 1-octanol, and 1-decanol), in two secondary alcohols (2-propanol and 2-butanol), and in one branched primary alcohol (2-methyl-1-propanol) at 298 K and atmospheric pressure.…”