The aim of this study was to conduct a thermodynamic analysts of the uptake of solvents into a model membrane as a precursor to skin transport studies. The investigation was designed so that the methodology may be applied to analyse data produced from measurement of the uptake of enhancers into skin. The uptake of a series of alcohols into polydimethylsiloxane (silicone) membranes in the temperature range 5-45 degrees C was examined. A thermodynamic analysis of the data was performed to provide fundamental insight into the uptake process. A simple structure activity relationship was found to exist for the uptake of alcohols with a carbon chain length greater than four, with additional methylene groups exponentially decreasing the equilibrium uptake Two separate straight lines were observed in the van't Hoff plot for the equilibrium solvent uptake above and below 16 degrees CThe two separate straight lines in the van't Hoff plot suggest a change in the mechanism of solvent uptake and solvent structure in the membrane above and below 16 degrees C. This is likely to have implications for the effect of the solvents on the partitioning of drugs into the membrane and will be used to provide insight into dynamic measurements of the effect of temperature on the transport of drug molecules in the same vehicles, across the membrane. The analysis described here should provide a useful methodology for investigating the uptake of solvents into model membranes (C) 2010 Elsevier B V All rights reserved

Heats of dissolution of a homologous series of m-alkoxy phenols in an osmotically stable isotonic solution and in the same media containing a suspension of Escherichia coli cells were obtained by a differential heat conduction batch calorimeter at 298 K. The calorimetric curves show an initial rapid endothermic dissolution of the solute, followed by an exothermic process. From the heats of solution, the heat of transfer (Q(trs)) of these compounds from the aqueous solution to the cells was calculated. The heat of transfer is exothermic and increases with the hydrophobicity of the compounds due to the biological consequences of the interaction process with the lipidic phase.

Isothermal calorimetry is becoming indispensable as a tool for the study of a wide variety of systems. As with all scientific instruments it is essential that robust calibration routines be developed in order to validate the data obtained. Chemical test reactions offer many advantages over (the traditionally used) joule effect heating methods, not least because they have the potential to validate instrument performance (i.e. they can be used to assess all aspects of calorimeter operation). In this work the results of a validation exercise, conducted by Thermal Hazard Technology as part of an installation routine, using the base catalysed hydrolysis of methyl paraben are discussed. In the case described, a systematic misreporting of the reported temperature of a calorimeter was identified, caused by an upgrade to the calorimeter's firmware, a discrepancy which may not have been noted using traditional electrical calibration methods and one which highlights the importance of both manufacturers and end-users adopting chemical test reactions into their test and validation routines.

Isothermal calorimetry is finding extensive application in a number of research areas. This popularity is reflected in the number of commercially available instruments which are capable of yielding a variety of thermodynamic and kinetic parameters. Whilst there has been much discussion of ways in which to validate any values returned from these instruments very little has been done quantitatively to compare the relative performances of different instruments. This paper highlights the use of a test and reference reaction quantitatively to compare the performance of three instruments (Thermometric TAM, THT µRC and a Setaram HSDSC III); the specifications of these instruments provide a range from high-sensitivity, long equilibration time to lower-sensitivity, short equilibration time. The comparison is made through a statistical analysis of values returned for the rate constant, enthalpy of reaction and activation energy for the base catalysed hydrolysis of methyl paraben. The statistical analysis from the data set discussed here indicates that there is no significant difference between the returned thermodynamic and kinetic parameters from the TAM and µRC. The analysis revealed however that the HSDSC returns values for the rate constant which are significantly different from both the TAM and µRC, although it is noted that this instrument was not specifically designed to operate in a step-isothermal mode and that it was possible to apply a correction to the data. In all cases the enthalpy data returned from all instruments were statistically similar although the µRC and HSDSC returned values which were, for the rate constant and activation energy, less precise than those obtained from the TAM. As well as highlighting the importance of using test and reference reactions, this study also shows that proper instrument selection is an important factor when designing a calorimetric experimental series.

Isothermal calorimetry is becoming indispensable as a tool for the study of a wide variety of systems. As with all scientific instruments it is essential that robust calibration routines be developed in order to validate the data obtained. Chemical test reactions offer many advantages over (the traditionally used) joule effect heating methods, not least because they have the potential to validate instrument performance (i.e. they can be used to assess all aspects of calorimeter operation). In this work the results of a validation exercise, conducted by Thermal Hazard Technology as part of an installation routine, using the base catalysed hydrolysis of methyl paraben are discussed. In the case described, a systematic misreporting of the reported temperature of a calorimeter was identified, caused by an upgrade to the calorimeter's firmware, a discrepancy which may not have been noted using traditional electrical calibration methods and one which highlights the importance of both manufacturers and end-users adopting chemical test reactions into their test and validation routines.

This paper describes the exploratory use of isothermal micro-calorimetry (IMC) to measure directly the heat flow produced as seeds age. Heat flow was recorded in primed and non-primed (control) seeds of Ranunculus sceleratus L., aged in a micro-calorimeter at 35°C at three different seed water contents [c. 0.12, 0.075 and 0.045 g H2O (g dw)−1]. The rate of heat flow and total heat generated (an indicator of extent of reaction) were generally greater in control seeds, which aged at a faster rate, than in primed seeds. Total heat generated over a given period also increased with increasing water content. The power–time curves did not indicate first- or second-order rate kinetics, consistent with the probability that seed ageing is complex and involves a number of reactions. Even after the capacity to germinate had ceased, there was a residual power signal. As a method, IMC gave consistent results using independent samples at different times. Therefore, short-term experiments at relatively high water contents and/or temperatures may have the potential to predict the relative longevity of seed-lots, at least within a species.

Isothermal calorimetry offers the potential to determine rapidly the stability of formulated pharmaceuticals because it is indifferent to physical form and sensitive enough to detect extremely small powers; ca. 50 nW at 25 °C. However, its use in this area is not widespread, principally because the power–time data obtained often comprise contributions from more than one process and are thus difficult to analyse quantitatively. In this work, we demonstrate how power–time data recorded for systems in which two components are degrading in parallel (in this case, binary mixtures of selected parabens) can be analysed using a kinetic-based model; the methodology allows the determination of the first-order rate constant and reaction enthalpy for each process, so long as one rate constant is at least twice the magnitude of the other. It was found that the reactions did not need to run to completion in order for the analysis to be successful; a minimum of 15 min of data were required for samples with one degrading component and a minimum of 4 h of data were required for samples with two degrading components. It was observed that the rate constants for paraben degradation in binary systems were significantly lower than expected. This was ascribed to the fact that the parabens degrade to a common product and is an important factor that should be accounted for when the two or more parabens are formulated together.

The swelling, as a function of temperature, of cationic (poly(N-isopropylacrylamide/methylenebisacrylamide/4-vinylpyridine) [poly(NIPAM/BA/4-VP] microgels (synthesized using different mole fractions of 4-VP), has been studied by photon correlation spectroscopy (PCS). Analysis of the PCS data showed that the volumes occupied by these microgels are constant, for each microgel, over a range of temperatures (320–333K). The volume occupied by a given microgel at 333K is hypothesized to be a property of the microgel itself. These data support the view that the microgel volume at 333K is a convenient and appropriate reference state. The limit (333K) volumes are constant and the same, within experimental error, for all the microgels. The particularly interesting observation made from this study is that the normalised volume data, at 333K, for all samples is similar to that of poly(NIPAM/BA) microgels. Furthermore, the normalised volume data illustrate well how the defined swelling ratio discriminates between the microgels in terms of their sensitivity to temperature. A thermodynamic approach, using van’t Hoff analysis, allows direct comparison of swelling as a function of temperature for these microgel systems. Importantly, entropy values undergo a change in sign from positive at low (288K) temperature to negative values at high (333K) temperature. In addition, the thermodynamic analysis suggests that at temperatures below the volume phase transition temperature (VPTT) of the microgel, interstitial solvent is similar to bulk solvent whereas this is not the case at temperatures above the VPTT.

This paper provides a pragmatic approach for calculation of equilibrium constants that have been determined from systems at equilibrium by measuring a component of the equilibrium at several (minimum of three) different temperatures. The paper builds on previous work that has shown by selecting appropriate temperatures so that the van’t Hoff isochore could be written in terms of the total amount of a measured analyte (Atotal) associated with the equilibrium, equilibrium constants could be determined. This paper describes a mathematical method that uses the linearity of the van’t Hoff plot, lnK versus 1/T as the basis to systematically test for an appropriate Atotal value and derive the best values of equilibrium constants. It will also show that this method is freed from constraints in choosing the study temperatures.

Transdermal drug delivery is gaining wider interest as a potential route for the delivery of pharmaceutical products. It offers several benefits over other routes of administration particularly the avoidance of first pass metabolism. However, by its very design skin is an extremely effective barrier to the ingress of foreign materials thus making it difficult to deliver therapeutic doses. There is considerable interest therefore in developing novel methods to improve bioavailability of drugs administered transdermally. Many of the proposed methods involve some invasive modification of the system or have some inherent stability problems. Here we discuss novel methods for the calculation of the thermodynamic parameters which govern transdermal drug delivery and investigate means by which these characteristics can be exploited in order to improve bioavailability of transdermal drugs.

A simple but novel thermodynamic model is presented, based upon van't Hoff analysis, for the reversible swelling behavior of colloidal microgels. The swelling, as a function of temperature, of poly(N-isopropylacrylamide/N,N'-methylenebisacrylamide) as well as poly(N-isopropylacrylamide/vinylpyridine/N,N'-methylenebisacrylamide) and poly(N-isopropylacrylamide/acrylic acid/N,N'-methylenebisacrylamide) microgel dispersions in H2O and D2O has been studied by photon correlation spectroscopy (PCS). PCS data was used to obtain the hydrodynamic diameter and hence the volume of the microgels (before and after reconstitution following freeze-drying) as a function of temperature. The choice of standard reference states, for analyzing the data attained, is discussed, and the one selected is that of the volume of the microgels at 333 K in H2O. For all microgels examined the volume, at this temperature, is shown to be independent of solvent (H2O, D2O). The derived data has allowed the exploration of a novel thermodynamic approach to the study of the swelling behavior of the microgels. The constant volume, at 333 K, for each of the polymer systems constituting the microgels is suggested to be an intrinsic property of the polymers themselves.

Recent papers have reported [Thermochim. Acta 399 (2003) 63; Thermochim. Acta, in press] the results of a preliminary inter/intra laboratory study into the suitability of the base-catalysed hydrolysis of methyl paraben as a test and reference reaction for isothermal flow-through calorimeters. It was shown that this reaction can be used to investigate the flow characteristics of the instrument being used. It has also allowed, for the first time, the calculation of accurate values for the rate constant and for the enthalpy change, ΔH (hereafter H (enthalpy) for simplicity) of reaction directly from the calorimetric data, free from assumption. These findings have been extended to permit the direct determination of Michaelis–Menten based kinetic parameters from calorimetric data again free from assumption (except that the system conforms to Michaelis–Menten kinetic theory). This paper describes the method used for such an analysis and reports the results of a preliminary study on the urea/urease enzymatic system.

This paper discusses the theory and experimental application of microcalorimetry to the study of solid state reactions of pharmaceutical importance. The practical example selected is that of formulated products containing benzoyl peroxide – a treatment for acne and athlete’s foot. A newly developed procedure for data analysis is outlined and preliminary results from chemometric-based analysis of complex solid state reaction schemes is presented. Finally, the microcalorimetric requirements for such stability studies are contrasted with the newly emerging multi-channel “chip calorimeters” that operate in the nano range (watts, material, concentration) with high throughput potential.

This paper reports a technique for heat conduction isothermal microcalorimeters, which allows, by means of a lowering apparatus, the sample and reference ampoules to be lowered very slowly from the pre-equilibration position to the measuring position. The purpose is to minimize the effect on (total) equilibration time arising from both the pre-equilibration time and the dissipation time (i.e. the time to dissipate the thermal shock which occurs when the vessels are lowered manually). Measurements using 3ml glass ampoules filled with water, as sample and reference, at 25 and 60°C, showed that the extent of thermal shock was drastically diminished as the lowering speed decreased, and that the associated heat quantity was reduced to less than 0.2mJ when lowering occurred over a period of more than 180s. The dissipation time, the time-period required to dissipate the thermal shock, was also shortened to less than 10min; the standard manual lowering procedure dissipation time being ca. 25min. In practice experimental measurements of the imidazole catalysed hydrolysis of triacetin and of the solid state oxidation of ascorbic acid showed that the dissipation time was not shortened when the initial power observed was more than 5μW, however, it was significantly shortened when the initial power observed was around ≤1μW. The proposed ampoule lowering procedure could be expected to bring about a saving in the total measurement time for reactions with low initial power, such as those associated with long-term stability studies of relatively stable pharmaceuticals. The described procedure also eliminates operator-induced effects associated with manual lowering of ampoules. In principle the device described also would permit automated loading protocols to be developed.