Stability assessment of pharmaceuticals by isothermal calorimetry: two component systems

Skaria, Cyrus V.; Gaisford, Simon; O'Neill, M; Buckton, Graham; Beezer, Anthony E.

doi:10.1016/j.ijpharm.2004.11.029

Cited by 29 publications

(21 citation statements)

References 20 publications

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confidence: 99%

“…[32] A previous determination of reaction enthalpy using ampoule-based calorimetric data and Equation (7) for the hydrolysis of ethyl paraben gave a value for DH 2 of (64.4 AE 1.3) (1SD, N = 3) kJ mol À1 . [32] Applying a hard modeling approach [Eq. (7)] to the present flow-through calorimetric data (single reaction runs 1 and 2) and using a nonlinear least-squares curve-fitting approach resulted in a value for DH 1 of (53.0 AE 0.1) kJ mol À1 and a value for DH 2 of (56.2 AE 0.1) kJ mol…”

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confidence: 99%

“…In the past, a hard modeling approach involving kinetic rate expressions has commonly been used with calorimetric data alone, from both methyl paraben hydrolysis [25,31,32] and ethyl paraben hydrolysis. [32] The general expression is given in Equation (7):…”

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confidence: 99%

“…[32] In that study, a kinetic-modelbased approach (hard modeling) was employed; however, it was not possible to decouple these two individual heats of reaction. Numerical difficulties will certainly arise when more parameters need to be determined simultaneously for two parallel reactions, especially when the rates of these reactions are rather similar.…”

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Combined Online Spectroscopic, Calorimetric, and Chemometric Analysis: Reaction Enthalpy Determinations in Single and Parallel Reactions

2009

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Calorimetry and signal processing: Vibrational spectroscopies, heat-flow microcalorimetry, and multivariate analysis are combined to decouple the reaction enthalpies of parallel reactions [picture: see text]. This methodology allows the evaluation of reaction enthalpy from complex systems without recourse to conventional kinetic modeling. Simultaneous in situ/online spectroscopy and heat-flow measurements as well as multivariate analyses are performed, apparently for the first time, to determine heats of reaction for single and parallel reactions. Two different vibrational spectroscopy techniques, namely Raman and FTIR spectroscopy, are used in conjunction with flow-through TAM III microcalorimetry. With respect to the spectroscopic analysis, the reaction spectra are first analyzed to determine the pure-component spectra and the corresponding concentrations without recourse to external calibration. With respect to the calorimetric analysis, a soft modeling approach is employed to determine the heats of reaction without recourse to any conventional kinetic models. This combined approach is implemented to determine the extents of reaction as well as the corresponding heats of reaction at 298.15 K and 0.1 MPa for a) the hydrolysis of acetic anhydride (single reaction) and b) the hydrolysis of methyl paraben and ethyl paraben in alkaline solution (both single and parallel reactions). In the latter case, the heat-flow contributions from the two simultaneous reactions are successfully decoupled. Taken together, these results demonstrate proof of concept for the present approach. The newly developed methodology appears to be quite general and particularly useful for investigating complex reaction systems. This is particularly true for multiple simultaneous reactions and reactions where the detailed kinetic expressions are not available, or cannot be easily determined. The use of extents of reaction is also very helpful where there is high variability in reaction rates, that is, due to the presence of impurities, changes in catalyst activity, or concentrations, temperature, and pH.

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Combined Online Spectroscopic, Calorimetric, and Chemometric Analysis: Reaction Enthalpy Determinations in Single and Parallel Reactions

2009

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“…Once the number and orders of individual processes are known, then reaction parameters can be recovered by classical analyses such as those we have already proposed. [1][2][3][4] From the perspective of pattern analysis, each component in the system will exhibit a unique maximum during the course of the reaction at a defined time which suggests that the data may be analyzed by a multivariate method if a suitable matrix can be generated. Multivariate data are easily generated in spectroscopic systems 14 (for instance, intensity as a function of wavenumber, time, pH, temperature, etc.).…”

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Application of Chemometric Analysis to Complexity in Isothermal Calorimetric Data

et al. 2007

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The interpretation of complexity in isothermal calorimetric data is demanding. The observed power signal is a composite of the powers arising from each of the individual events occurring (which can involve physical, as well as chemical, change). The challenge, therefore, lies in deconvoluting the observed data into their component parts. Here, we discuss the potential use of chemometric analysis, because it offers the significant advantage of being model-free, using principal component analysis to deconvolute data. Using model data, we discovered that the software required a minimum trivariate data matrix to be constructed. Two variables, power and time, were available from the raw data. Selection of a third variable was more problematic, but it was found that by running multiple experiments the small variation in the number of moles of compound in each experiment was sufficient to allow a successful analysis. In general we noted that it required a minimum 2n + 2 repeat experiments to allow analysis (where n is the number of reaction processes). The data outputted from the chemometric software were of the form intensity (arbitrary units) versus time, reflecting the fact that the software was written for analysis of spectroscopic data. We provide a mathematical treatment of the data that allows recovery of both reaction enthalpy and rate constants. The study demonstrates that chemometric analysis is a promising approach for the interpretation of complex calorimetric data.

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Microcalorimetry and Related Techniques

Cooper¹

2007

Handbook of Biosensors and Biochips

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Direct determination of heat effects from biomolecular processes has significant potential for noninvasive biosensor and biomolecular analysis procedures requiring no additional labeling or attachment procedures. This chapter describes current instrumental techniques in isothermal titration (ITC), differential scanning (DSC), pressure perturbation (PPC) and photocalorimetry, together with examples of some relevant applications. Some developments and associated problems in calorimeter‐on‐a‐chip and related devices are discussed.

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Stability assessment of pharmaceuticals by isothermal calorimetry: two component systems

Cited by 29 publications

References 20 publications

Combined Online Spectroscopic, Calorimetric, and Chemometric Analysis: Reaction Enthalpy Determinations in Single and Parallel Reactions

Combined Online Spectroscopic, Calorimetric, and Chemometric Analysis: Reaction Enthalpy Determinations in Single and Parallel Reactions

Application of Chemometric Analysis to Complexity in Isothermal Calorimetric Data

Microcalorimetry and Related Techniques

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