M. A. Pena

Further Numerical Analyses on the Solubility of Sulfapyridine in Ethanol + Water Mixtures

Background: Dissolution thermodynamic quantities of sulfapyridine (SP) have been reported in the literature for aqueous alcoholic mixtures. Nevertheless, no attempts to evaluate the preferential solvation of this drug in this binary system, have been reported. In this way, the inverse Kirkwood-Buff integrals (IKBI) were used to evaluate this behavior in solution. Methods: Solubility data for SP dissolved in binary ethanol (EtOH) + water mixtures at various temperatures were mathematically represented using the Jouyban-Acree (J-A) model. The preferential solvation parameters of SP by EtOH (δx1,3) in EtOH + water mixtures were obtained from some thermodynamic properties of the mixtures by means of the IKBI method. Results: Solubility of SP in EtOH + water mixtures is adequately described by the J-A model in second order. Moreover, SP is sensitive to specific solvation effects, so the δx1,3 values are negative in water-rich and EtOH-rich mixtures indicating preferential solvation by water in these mixtures. By contrary, δx1,3 values are positive in the range 0.24 < x1 < 0.53 indicating preferential solvation by EtOH in these mixtures. Conclusion: It can be assumed that in water-rich mixtures the hydrophobic hydration around the aromatic rings plays a relevant role in the solvation. The higher drug solvation by EtOH in mixtures of similar solvent proportions could be due to polarity effects. Moreover, in EtOH + water mixtures SP could be acting as a Lewis acid with the EtOH molecules and in EtOH-rich mixtures the drug could be acting as a Lewis base with water molecules.

Preferential solvation of some n-alkyl p-substituted benzoates in propylene glycol + water cosolvent mixtures

The preferential solvation parameters by propylene glycol (PG) of the homologous series of the n-alkyl esters of p-hydroxybenzoic and p-aminobenzoic acids, namely, methyl, ethyl, propyl and butyl derivatives, were derived from their thermodynamic properties of solution by means of the inverse Kirkwood–Buff integrals (IKBI) method. The preferential solvation parameters by the cosolvent, δx1,3, are negative in water-rich mixtures, but positive in PG-rich mixtures, and the relative magnitudes of δx1,3 are proportional to the alkyl chain length despite of the solvent involved in the preferential solvation, i.e. PG or water. It is possible that the hydrophobic hydration around aromatic ring and/or methylene groups plays a relevant role in the drugs solvation in water-rich mixtures. The more solvation by PG in PG-rich mixtures could be due mainly to polarity effects and acidic behaviour of the hydroxyl or amine groups of the compounds in front to the more basic solvent present in the mixtures, i.e. PG.

Preferential Solvation of Indomethacin in Some Aqueous Co-Solvent Mixtures

The preferential solvation parameters for indomethacin (IMC) in ethanol (EtOH) + water and propylene glycol (PG) + water binary mixtures were obtained from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals (IKBI) and the quasi-lattice quasi-chemical (QLQC) methods. According to IKBI method, the preferential solvation parameter by co-solvents, (δx1,3), is negative in the water-rich mixtures of both binary systems but positive in the other compositions at temperatures of 293.15, 303.15, and 313.15 K. It is conjecturable that in water-rich mixtures the hydrophobic hydration around the aromatic rings and methyl groups of the drug plays a relevant role in the solvation. The higher drug solvation by co-solvent in mixtures of similar solvent proportion and in co-solvent-rich mixtures could be due mainly to polarity effects. Here IMC would be acting as a Lewis acid with the EtOH or PG molecules because these co-solvents are more basic than water.

Extended Hildebrand solubility approach applied to some sulphonamides in propylene glycol + water mixtures

Extended Hildebrand solubility approach (EHSA) was applied to evaluate the solubility of sulphanilamide, sulphapyridine and sulphamethizole in some propylene glycol + water mixtures at 298.15 K. Reported experimental solubility and some properties of fusion of this drug were used for the calculations. In particular, a good predictive character of EHSA has been found by using a regular polynomial in order five of the interaction parameter W as a function of the solubility parameter of solvent mixtures free of drug. Nevertheless, the predictive character of EHSA is the same as the one obtained by direct correlation between drug solubilities and the same descriptor of polarity of the co-solvent mixtures.

Raman spectral signatures for the differentiation of benzodiazepine drugs

The identification of benzodiazepine drugs is important in the forensics field because they are used in drug-facilitated crimes. Raman spectroscopy has been proven as a non-invasive, fast and reliable technique highly promising for the analysis of drug products. Until recently, attention has been paid to active ingredients, but the spectral drug product signature has rarely been used in spite of having potential valuable information. In this work, confocal Raman microscopy was used to obtain the spectral signature of the most widely used benzodiazepine products. Firstly, the study aimed at determining appropriate Raman mapping spectra to obtain each benzodiazepine signature with low sampling error. Then, PCA scores and loadings showed that the variability, measured on the variance, among batches of the same benzodiazepine drug was similar to the variability of the spectral signature of the same tablet (or capsule content) and the same batch, mainly attributed to the heterogeneity of such drug products. Interestingly, differentiation among doses of the same active ingredient (AI), benzodiazepine drugs with different AIs manufactured by the same pharmaceutical company, and drugs with the same AI but manufactured by different companies were demonstrated. It is remarkable that for low doses, the active ingredient is almost absent of the spectral signature, but the differentiation is mainly achieved by excipients. As a consequence, the spectral signature obtained by confocal Raman microscopy can be used for discriminating among these benzodiazepine drugs without requiring a clearly identifiable band related to the active ingredient in the corresponding Raman spectra.

Preferential solvation of indomethacin in 1,4- dioxane + water mixtures according to the inverse Kirkwood–Buff integrals method

ABSTRACT The preferential solvation parameters (δx1,3) of indomethacin (IMC) in 1,4-dioxane + water binary mixtures were derived from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals method. δx1,3 is negative in water-rich and 1,4-dioxane-rich mixtures but positive in cosolvent compositions from 0.17 to 0.69 in mole fraction of 1,4-dioxane at 298.15 K. It is conjecturable that in water-rich mixtures, the hydrophobic hydration around the aromatic and methyl groups of the drug plays a relevant role in the solvation. The higher solvation by 1,4-dioxane in mixtures of similar cosolvent compositions could be mainly due to polarity effects. Finally, the preference of this drug for water in 1,4-dioxane-rich mixtures could be explained in terms of the higher acidic behavior of water molecules interacting with the hydrogen-acceptor groups present in IMC.

Extended Hildebrand solubility approach applied to some sulphapyrimidines in some {methanol (1) + water (2)} mixtures

ABSTRACT Extended Hildebrand solubility approach (EHSA) was applied to analyse the equilibrium solubility of sulphadiazine, sulphamerazine and sulphamethazine in some {methanol (1) + water (2)} mixtures at 298.15K. Reported experimental solubilities and some fusion properties of these drugs were used for EHSA calculations. A good predictive character of EHSA (with mean deviations lower than 4.0%) was found by using regular polynomials in order 4 when correlating the interaction parameter (W) and the Hildebrand solubility parameter of solvent mixtures free of drug (δ1+2). Nevertheless, the predictive character of EHSA was almost the same as obtained when logarithmic drug solubilities (log x3) were correlated with δ1+2.

Equilibrium solubility and apparent specific volume of lidocaine.HCl.H2O in some {cosolvent (1) + water (2)} mixtures at 298.2 K

ABSTRACT Lidocaine.HCl is the most widely used anaesthetic drug in pharmaceuticals intended for local administration. Solubility data of this drug in aqueous cosolvent mixtures is not abundant. The main objective of this research was to determine and correlate the equilibrium solubility of lidocaine.HCl monohydrate in some {cosolvent (1) + water (2)} mixtures at 298.2 K. Cosolvents were polyethylene glycol 200 (PEG 200), ethanol and propylene glycol. Classical shaken-flask method was used to determine isothermal solubility. Concentration measurements were performed by means of electrical conductivity determinations after adequate aqueous dilutions. Solubility of lidocaine.HCl.H2O decreases non-linearly with the addition of cosolvent to water in almost all mixtures compositions. Jouyban–Acree model correlates solubility values with the mixtures composition for all cosolvent systems. Apparent specific volume of this drug was also calculated from density and mixtures compositions.

Extended Hildebrand solubility approach applied to sulphadiazine, sulphamerazine and sulphamethazine in some {1-propanol (1) + water (2)} mixtures at 298.15 K

ABSTRACT Extended Hildebrand solubility approach (EHSA) was applied in this research to analyse the equilibrium solubility of sulphadiazine, sulphamerazine and sulphamethazine in some {1-propanol (1) + water (2)} mixtures at 298.15 K. Reported experimental solubilities and some fusion properties of these drugs were used for EHSA calculations. A good predictive character of EHSA (with mean deviations lower than 4.0%) was found by using regular polynomials in order five when correlating the interaction parameter (W) and the Hildebrand solubility parameter of solvent mixtures free of drug (δ1+2). Nevertheless, the predictive character of EHSA was almost the same as obtained when logarithmic drug solubilities (log x3) were correlated with δ1+2 by using a fifth-degree regular polynomial.

Interventions to enhance the teaching of toxicology at a UK University

Following the recent communication from the European Societies of Toxicology (EUROTOX) advising that toxicology training and expertise is being eroded in the European Union, we have reviewed the teaching status of this subject in all the bioscience undergraduate courses offered at De Montfort University (DMU, UK). The courses reviewed were: Biomedical Science, Health and Wellbeing in Society, Speech and Language Therapy, Medical Science, Pharmaceutical and Cosmetic Science, Forensic Science and Pharmacy. None of these courses dedicate a complete module to the study of toxicology although they teach some aspects of toxicology following the subject-specific threshold standards described by the UK Quality Assurance Agency for Higher Education. Similar results are found in other UK Universities, although a comprehensive study on the status of toxicology teaching is needed. We have not found any undergraduate courses currently offered in the UK that contained the word “toxicology” in their title. These results are in agreement with EUROTOX, which indicated that toxicology has been generally integrated into other bioscience disciplines and is mainly offered as part of a taught postgraduate degree programme in Europe. Owing to these observations, our teaching group is performing different strategies to enhance the teaching of toxicology at DMU as we consider that the learning of this science is critically important to enable future health professionals to protect human health. These strategies included the development of specialised teaching/workshop sessions in toxicology that can be easily included in any undergraduate bioscience module. Thus, during 2016/17 we collected comprehensive feedback (during an Erasmus+ mobility grant for academics) from human health students about their views on the teaching of toxicology and one of the specialised workshops in a programme that does not offer a module in toxicology (BMedSci Medical Science, DMU) and one that does (MPharm. Pharmacy, University of San Pablo CEU, Spain). A high proportion of the students consulted requested more teaching of toxicology or the introduction of more specialised toxicology in their programmes. Thus, 85% of second year BMedSci students indicated that they would like to receive more toxicology training. Also, 42.9% (57.1% neither agree nor disagree) of fourth year MPharm. Students suggested the incorporation of specialised environmental toxicology workshops within their course and all of them considered the environmental toxicology training relevant to their general toxicology module. Other strategies implemented include the enhancement of research in toxicology in our university by offering final projects on these topics to undergraduate and postgraduate students, as well as completion of PhDs. Finally, DMU has recently recruited two toxicologists as academic staff, allowing us to promote the teaching/research of toxicology as well as exploring the possibility of developing postgraduate content for the teaching of toxicology. More efforts should be considered to enhance the teaching of this subject in any bioscience programme, as the current status of toxicology in the UK has been eroded.