Thermodynamics of partitioning and solvation of ketoprofen in some organic solvent: buffer and liposome systems

A termodinâmica da partição de cetoprofeno (KTP) foi estudada em diferentes sistemas solvente/tampão, tais como ciclo-hexano (CH/W), octanol (ROH/W), miristato de isopropila (IPM/W), clorofórmio (CLF/W), assim como em lipossomas de dimiristoil-fosfatidilcolina (DMPC) e de dipalmitoil-fosfatidilcolina (DPPC). Em todos os casos, os coeficientes racionais da partição (K X O/w) foram maiores que a unidade, conseqüentemente as energias livres de transferência padrão foram negativas, o que indica afinidade elevada de KTP para meios orgânicos. Os valores K X O/w foram aproximadamente 85 vezes maiores no sistema ROH/W em relação ao sistema CH/W, indicando-se, assim, alta contribuição da ligação hidrogênio sobre a partição. No entanto, para os sistemas IPM/W e CLF/W os valores K X O/w foram somente três ou quatro vezes menores que aqueles observados em ROH/W. De outra parte, os valores K X O/w foram aproximadamente 75 ou 150 vezes maiores nos lipossomas, comparados ao sistema ROH/W, segundo o caso, o que indica grau elevado de imobilização de KTP nas bicamadas e/ou contribuição eletrostática sobre a partição. Em todos os casos, as entalpias e as entropias padrão de transferência de KTP desde a água até os meios orgânicos foram positivas indicando algum grau de participação da hidratação hidrofóbica nos processos de partição. Finalmente, usando dados previamente relatados para o processo de solvatação de KTP na água, foram calculadas as funções termodinâmicas associadas com os processos de solvatação de KTP em todas as fases orgânicas avaliadas.The ketoprofen (KTP) partitioning thermodynamics was studied in different solvent/buffer systems such as cyclohexane (CH/W), octanol (ROH/W), isopropyl myristate (IPM/W), chloroform (CLF/W); as well as in dimyristoyl phosphatidylcholine (DMPC) and dipalmitoyl phosphatidylcholine (DPPC) liposome systems. In all cases, the rational partition coefficients (K X O/w) were greater than unit; therefore standard transfer free energies were negative in sign indicating a high affinity of KTP for organic media. K X O/w values were approximately eightyfive-fold higher in the ROH/W system regarding the CH/W system, thus indicating a high degree of hydrogen bonding contribution to partitioning. While in the case of IPM/W and CLF/W systems, K X O/w values were approximately only three or four-fold lower than those observed in ROH/W. On the other hand, K X O/w values were approximately seventy-five or one hundred fifty-fold higher in the liposomes compared to ROH/W system indicating a high degree of bilayers immobilization and/or an electrostatic contribution to partitioning. In all cases, standard transfer enthalpies and entropies of KTP from water to organic media were positive in sign indicating some degree of participation of the hydrophobic hydration on the partitioning processes. Finally, by using the reported data for solvation of KTP in water, the associated thermodynamic functions for KTP solvation in all tested organic phases were also calculated

Thermodynamic analysis of the solubility of propranolol-HCl in ethanol + water mixtures

Propranolol-HCl (PPN-HCl) is a non selective β-adrenergic blocker widely used in therapeutics. Nevertheless, their physicochemical properties in aqueous media have not been adequately studied. In this context, by using the van't Hoff and Gibbs equations the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution for this drug in ethanol (EtOH) + water (W) cosolvent mixtures, were evaluated from solubility data determined at several temperatures. The solubility was the greatest in the mixtures with 0.60 or 0.70 in mass fraction of EtOH and the lowest in neat W (or neat EtOH, as well) at almost all the temperatures studied. This behavior shows the cosolvent effect present for this electrolyte drug in this solvent system. By means of enthalpy-entropy compensation analysis, non-linear ΔH soln 0-app vs. ΔG soln 0-app plot with negative slope from water up to 0.10 in mass fraction of EtOH and positive slope from 0.10 to 0.60 in mass fraction of EtOH. Accordingly to this result, it follows that the dominant mechanism for the solubility of PPN-HCl in water-rich mixtures is the entropy, probably due to water-structure loosing around the drug's non-polar moieties by EtOH molecules, whereas, between 0.10 and 0.60 in mass fraction of EtOH the dominant mechanism is the enthalpy probably due to drug solvation increase by EtOH molecules. Ultimately, beyond this composition the behavior was more complex, and therefore, the ionic and molecular events involved in the drug dissolution in ethanol-rich mixtures are unclear.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Thermodynamic analysis of the solubility of propranolol-HCl in ethanol + water mixtures

Propranolol-HCl (PPN-HCl) is a non selective β-adrenergic blocker widely used in therapeutics. Nevertheless, their physicochemical properties in aqueous media have not been adequately studied. In this context, by using the van't Hoff and Gibbs equations the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution for this drug in ethanol (EtOH) + water (W) cosolvent mixtures, were evaluated from solubility data determined at several temperatures. The solubility was the greatest in the mixtures with 0.60 or 0.70 in mass fraction of EtOH and the lowest in neat W (or neat EtOH, as well) at almost all the temperatures studied. This behavior shows the cosolvent effect present for this electrolyte drug in this solvent system. By means of enthalpy-entropy compensation analysis, non-linear ΔH soln 0-app vs. ΔG soln 0-app plot with negative slope from water up to 0.10 in mass fraction of EtOH and positive slope from 0.10 to 0.60 in mass fraction of EtOH. Accordingly to this result, it follows that the dominant mechanism for the solubility of PPN-HCl in water-rich mixtures is the entropy, probably due to water-structure loosing around the drug's non-polar moieties by EtOH molecules, whereas, between 0.10 and 0.60 in mass fraction of EtOH the dominant mechanism is the enthalpy probably due to drug solvation increase by EtOH molecules. Ultimately, beyond this composition the behavior was more complex, and therefore, the ionic and molecular events involved in the drug dissolution in ethanol-rich mixtures are unclear.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Salmonella in free-ranging quokkas (Setonix brachyurus) from Rottnest Island and the mainland of Western Australia

Salmonella is a genus of Gram-negative, motile, and facultative anaerobic bacteria with a worldwide distribution that contaminates multiple substrates (vegetation, food, soil, and water) and inhabits the gastrointestinal tract of birds, reptiles, and mammals, including humans. Rottnest Island is a popular tourist destination and is abundantly inhabited by quokkas (Setonix brachyurus), a charismatic small wallaby. Current data on the association between Salmonella and quokkas on Rottnest Island are outdated by approximately 30 years. Additionally, previous studies on quokkas on this island and mainland Western Australia did not perform physical examinations or any diagnostic tests. The aim of the project was to assess the prevalence of Salmonella spp. in quokkas from Rottnest Island and mainland Western Australia and correlate the presence of the bacterium with the health of the animal. Ninety-two quokkas from Rottnest Island (n = 71) and populations on the mainland (n = 21) were screened for Salmonella, and a prevalence of 47.9% and 4.8%, respectively, was determined. A total of 16 serovars were identified from 37 isolates; five of these serovars had previously not been described in the quokka. Salmonella appeared to have an effect on the haematology and blood chemistry of quokkas on Rottnest Island consistent with subclinical salmonellosis. The health of Rottnest Island quokkas, and their potential impact on the health of the visitors to the island, should continue to be monitored carefully

Study of some volumetric properties of the pharmaceutical model solvent system ethanol + ethyl acetate at several temperatures

The binary solvent system ethanol + ethyl acetate is widely used in the pharmaceutical sciences as a versatile model for studying the solubility of drugs. In this context, the excess molar volumes and the partial molar volumes of components were investigated from density measurements on the entire range of mass fractions, for this system at 293.15 K, 298.15 K, 303.15 K, 308.15 K, and 313.15 K. The excess molar volumes were fitted by Redlich-Kister equation by using third degree polynomials and compared with those reported in the literature for other solvent systems. The system tested exhibited positive excess volumes (up to 0.18 cm3 mol-1 at 313.15 K), probably due to weak interactions, like dispersion forces, between unlike molecules or, some differences in the molar volumes of pure components. The effect of temperature on the different volumetric properties studied was also analyzed.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Solution Thermodynamics of Lysine Clonixinate in Some Ethanol + Water Mixtures

The solubility of lysine clonixinate (LysClon) in several ethanol + water mixtures was determined at 293.15 to 313.15 K. The thermodynamic functions, Gibbs energy, enthalpy, and entropy of solution and of mixing were obtained from these solubility data by using the van’t Hoff and Gibbs equations. In general this drug exhibit good solubility and the greatest value was obtained in the mixture 0.60 in mass fraction of ethanol. A non-linear enthalpy–entropy relationship was observed from a plot of enthalpy vs. Gibbs energy of solution. Accordingly, the driving mechanism for LysClon solubility in water-rich and ethanol-rich mixtures is the entropy, probably due to water-structure losing around the drug non-polar moieties by ethanol or increased ionic solvation; whereas, in the medium composition mixtures the driving mechanism is the enthalpy, probably due to LysClon solvation increase by the co-solvent molecules.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Thermodynamic study of the solubility of ibuprofen in acetone and dichloromethane

Thermodynamic functions, Gibbs energy, enthalpy and entropy for the solution processes of ibuprofen (IBP) in acetone and dichloromethane (DCM) were calculated from solubility values obtained at temperatures ranging from 293.15 K to 313.15 K. The respective thermodynamic functions for mixing and solvation processes as well as the activity coefficients for the solute were calculated. IBP solubility was high and proved similar in both solvents but was greater in DCM than acetone. In addition, the thermodynamic quantities for the transfer process of this drug from cyclohexane to the organic solvents were also calculated in order to estimate the contributions of hydrogen-bonds or of other dipolar interactions. The results were discussed in terms of solute-solvent interactions.As funções termodinâmicas, energia de Gibbs, entalpia e entropia dos processos de solução de ibuprofeno (IBP) em acetona e em diclorometano (DCM) foram calculadas a partir dos valores de solubilidade, obtidos em intervalos de temperatura de 293,15 K a 313,15 K. As funções termodinâmicas respectivas para os processos de mistura e solvatação e os coeficientes de atividade para o soluto também foram calculados. A solubilidade do IBP foi grande e semelhante em ambos os solventes, mas, maior em DCM do que em acetona. Em adição, as quantidades termodinâmicas relativas ao processo de transferência desse fármaco do cicloexano para os solventes orgânicos foram, também, calculadas com o objetivo de estimar as contribuições devidas às ligações de hidrogênio ou a outras interações dipolares. Os resultados foram discutidos nos termos das interações soluto-solvente

Solution Thermodynamics of Lysine Clonixinate in Some Ethanol + Water Mixtures

The solubility of lysine clonixinate (LysClon) in several ethanol + water mixtures was determined at 293.15 to 313.15 K. The thermodynamic functions, Gibbs energy, enthalpy, and entropy of solution and of mixing were obtained from these solubility data by using the van’t Hoff and Gibbs equations. In general this drug exhibit good solubility and the greatest value was obtained in the mixture 0.60 in mass fraction of ethanol. A non-linear enthalpy–entropy relationship was observed from a plot of enthalpy vs. Gibbs energy of solution. Accordingly, the driving mechanism for LysClon solubility in water-rich and ethanol-rich mixtures is the entropy, probably due to water-structure losing around the drug non-polar moieties by ethanol or increased ionic solvation; whereas, in the medium composition mixtures the driving mechanism is the enthalpy, probably due to LysClon solvation increase by the co-solvent molecules.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Study of some volumetric properties of the pharmaceutical model solvent system ethanol + ethyl acetate at several temperatures

The binary solvent system ethanol + ethyl acetate is widely used in the pharmaceutical sciences as a versatile model for studying the solubility of drugs. In this context, the excess molar volumes and the partial molar volumes of components were investigated from density measurements on the entire range of mass fractions, for this system at 293.15 K, 298.15 K, 303.15 K, 308.15 K, and 313.15 K. The excess molar volumes were fitted by Redlich-Kister equation by using third degree polynomials and compared with those reported in the literature for other solvent systems. The system tested exhibited positive excess volumes (up to 0.18 cm3 mol-1 at 313.15 K), probably due to weak interactions, like dispersion forces, between unlike molecules or, some differences in the molar volumes of pure components. The effect of temperature on the different volumetric properties studied was also analyzed.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Preferential Solvation of Acetaminophen in Propylene Glycol + Water Co-Solvent Mixtures

The preferential solvation parameters defined as the differences between the local mole fraction of solvents around analgesic drug acetaminophen and those for the bulk co-solvent composition in propylene glycol + water mixtures were derived from their thermodynamic properties by means of the inverse Kirkwood-Buff integrals (IKBI) and the quasi-lattice-quasi-chemical (QLQC) methods. It is found that acetaminophen is sensitive to solvation effects, so according to IKBI method the preferential solvation parameter δ´xPG,A, is negative in water-rich mixtures but positive in medium compositions and in co-solvent-rich mixtures. It is conjecturable that in water-rich mixtures the hydrophobic hydration around the aromatic ring and methyl group present in the drug plays a relevant role in the solvation. The bigger drug solvation by co-solvent in mixtures of similar solvent proportions and in propylene glycol-rich mixtures could be due mainly to polarity effects. Otherwise, according to QLQC method, this drug is preferentially solvated by the co-solvent in all the mixtures