Siegfried Lindenbaum

Thermodynamic studies on the gel-sol transition of some pluronic polyols

Studies have been carried out on a number of pluronic polyols with the aim of determining factors which influence the transition temperature of the hydrogels. The gel-sol transition temperatures, Tm, were measured for aqueous solutions of the polyols with and without additives such as sodium chloride, potassium chloride, urea, ethanol, sodium sulfate and sodium dodecylsulfate. A linear relationship was found between the logarithm of the pluronic polyol concentration and the reciprocal of the gel-sol transition temperature. Although no linear relationship was observed between log Mw (molecular weight) and the reciprocal of the gel-sol transition temperature for all polymers, such a relationship does seem to exist among the polymers having the same ratio of poly(oxypropylene) to poly(oxyethylene) units per mole of polymer, (P/E ratio). All of the pluronic polyols studied showed endothermic enthalpy change for the sol-gel process. These results were substantiated with data from calorimetric studies. The driving force for thermal gelation is a result of the large entropic change. Neither Δ Hgelo (for sol-gel) nor ΔSgelo seem to correlate with the molecular weight of the polymer, per se; however, the number of poly(oxypropylene) units per mole of polymer plays a major role in the gelation process. The presence of sodium chloride, potassium chloride and sodium sulfate decreased the transition temperature whereas the opposite effect was observed with urea, alcohol and sodium dodecylsulfate. The enthalpy of gel formation was not

Studies on complexation between β-cyclodextrin and bile salts

Abstract The thermodynamic parameters for the inclusion complexation of β-cyclodextrin and thirteen bile salts have been measured with flow microcalorimetry. The results show that most of the bile salts studied here form 1:1 complexes with the exception of deoxycholate and its conjugates which form 1:1 plus 1:2 complexes. The complexation affinities follow the order: deoxycholates > ursodeoxycholates ≈ chenodeoxycholates > cholates ≈ dehydrocholate. The inclusion modes were established with H-NMR for β-cyclodextrin and three bile salts. The thermodynamic data are consistent with the complex structures.

The binding of Ca2+ to taurine- and glycine-conjugated bile salt micelles

The binding of Ca2+ to micelles of glycine and taurine bile acid conjugates was studied using a Ca2+-specific electrode. An investigation of the effect of buffer concentration, pH, added electrolyte and lecithin was also carried out. The observed results indicate that the binding of Ca2+ to bile salt micelles is dependent on both the number of hydroxyl groups on the steroid nucleus as well as on the nature of the head conjugating group, viz. glycine or taurine. It is speculated that the binding of Ca2+ to bile salt micelles may act as one of the mechanisms to lower Ca2+ activity in bile and thus reduce its tendency to precipitate as insoluble calcium salts and further growth into gallstones.

High resolution spectroscopic evidence and solution calorimetry studies on the polymorphs of enalapril maleate

Abstract Enalapril maleate, a potent angiotensin converting enzyme inhibitor, exists as polymorphs, Form I and Form II. X-Ray powder diffraction measurements have shown slightly different patterns. Differential scanning calorimetric thermograms failed to show any significant differences during melting. High resolution spectroscopic techniques, including solid state carbon-13 NMR, Fourier-transform IR and Raman, detect differences between Form I and Form II. Heats of solution data obtained also indicate measurable energy differences. It was concluded that these two polymorphic forms of enalapril maleate are energetically very similar. Virtual equivalence of in vitro dissolution rate was obtained from formulations of enalapril maleate made from either Form I, or Form II, or mixtures.

A quantitative circular dichroic investigation of the binding of the enantiomers of ibuprofen and naproxen to human serum albumin

The binding constants for racemic, R and S naproxen and ibuprofen to human serum albumin have been determined by a circular dichroic technique. The ibuprofens and naproxens show no measurable extrinsic optical activity on interaction with the protein, and so the extrinsic Cotton effect shown following the diazepam-albumin interaction is used as a probe. The presence of the drugs reduce the amount of diazepam bound as shown by the interaction is used as a probe. The presence of the drugs reduce the amount of diazepam bound as shown by the reduced size of the induced ellipticity. The calculated primary binding constants show that the S form of both drugs bind to the albumin more tightly than the R form and that the racemic forms bind less tightly than either enantiomer.

Solid-state stability studies of 13-cis-retinoic acid and all-trans-retinoic acid using microcalorimetry and HPLC analysis

The solid-state stabilities of 13-cis-retinoic acid and all-trans-retinoic acid in the presence and absence of oxygen were investigated. The samples were first evaluated using microcalorimetry. The rate laws of different samples under different conditions were deduced from the shapes of the heat flow curves, and the activation energies of the reactions were determined from Arrhenius plots. Under an air atmosphere, the decomposition of 13-cis-retinoic acid is an autocatalytic reaction, while all-trans-retinoic acid undergoes a zero-order process. The degradation of the two compounds at a selected elevated temperature was also determined utilizing HPLC analysis. This technique confirmed the decomposition kinetics. Hence, their half-lives and shelf lives at room temperature could be calculated. Under a nitrogen atmosphere, the microcalorimetric experiment showed a first-order phenomenon for both samples, but HPLC analysis showed no degradation, suggesting that the two samples, in the absence of oxygen, undergo only a physical change.

Thermodynamics of aqueous bile salt solutions: Heat capacity, enthalpy and entropy of dilution

Heat capacity data at various temperatures and enthalpies of dilution at 25°C are reported for aqueous bile salt solutions. The apparent molal heat contentsφL have been combined with osmotic and activity coefficients to obtain the excess molal entropies. Measurements of some of these properties have also been carried out with the anionic detergent sodium dodecylsulfate so that the bile salt micellization process may be compared with that of a classical detergent. The observed data have been interpreted in terms of the hydrophobic association properties of bile salts in aqueous solution.

Stability testing of pharmaceuticals by isothermal heat conduction calorimetry: Ampicillin in aqueous solution

Abstract The utility of isothermal heat conduction calorimetry for the study of stability of pharmaceuticals in solution is demonstrated in this study. The rate of heat evolution is measured as a function of the concentration of ampicillin, pH and the temperature. The pseudo first-order reaction rate constants, k , for the hydrolysis reaction are calculated from the variation of the heat evolution with time. The pH-rate profile for this reaction, as determined from the calorimetric data, is shown to correlate well with the literature data determined by other standard analytical methodology. The molal enthalpy of reaction was also calculated as function of pH and temperature.

The Effect of Octanoic Acid on the Binding of the Enantiomers of Ibuprofen and Naproxen to Human Serum Albumin: A Chromatographic Implication

AbstractPurpose. The heats of reaction between the enantiomers and racemates of ibuprofen and naproxen and human serum albumin (HSA) are to be measured with and without the addition of octanoic acid. The effects of octanoic acid on the free energies of interaction between the drugs and HSA is to be determined and compared to that estimated from theoretical equations. Methods. The heats of reaction have been measured directly by flow microcalorimetry. Results. The data showed that octanoic acid lowered the 1:1 binding constants for all the drug-HSA interactions investigated. The effect of octanoic acid was greater on the R than on the S forms of the drugs as shown by the differences in free energies of interaction in the presence and absence of octanoic acid. Conclusions. The increased free energy differences for the binding of the enantiomers of both drugs to HSA in the presence of octanoic acid is closer to the value deemed to be necessary for the separation of enantiomers by Davenkov, and shows the importance of the addition of octanoic acid to the mobile phase in the separation of these enantiomers on immobilized albumin columns.

Determination of the kinetics of degradation of 13-cis-retinoic acid and all-trans-retinoic acid in solution☆

The degradations of 13-cis-retinoic acid and all-trans-retinoic acid in an organic solvent were determined with an HPLC assay. The degradation curves at 70, 50 and 37 degrees C all showed autocatalytic characteristics for both isomers. For this kind of complex reaction, the usual method cannot be used to estimate the shelf-lives and half-lives at room temperature. In this work a new method was developed to directly calculate the shelf-lives and half-lives. From this equation the activation energy was found to change as the multiple step reaction progressed.