Calorimetric determination of rate constants and enthalpy changes for zero-order reactions.

Calorimetry is a general method for determination of the rates of zero-order processes, but analysis of the data for the rate constant and reaction enthalpy is difficult because these occur as a product in the rate equation so evaluation of one requires knowledge of the other. Three methods for evaluation of both parameters, without prior knowledge, are illustrated with examples and compared with literature data. Method 1 requires the reaction to be studied in two buffers with different enthalpies of ionization. Method 2 is based on calculation of reaction enthalpy from group additivity functions. Method 3 applies when reaction progresses to completion. The methods are applied to the enzymatic hydrolysis of urea, the hydrolysis of acetylsalicylic acid, and the photodegradation of nifedipine, respectively.

LED-array photocalorimetry: instrument design and application to photostability of nifedipine.

A photocalorimeter was designed to analyse quantitatively the photostability of pharmaceuticals. Its application is demonstrated with reference to two solution phase test systems; the photodegradations of 2-nitrobenzaldehyde (2-NB) and nifedipine. Light emitting diode (LED) arrays were used to illuminate the sample and reference channels of the calorimeter. Five LEDs were used to create an array from 360 to 700nm. A power supply system was constructed that zeroed the instrument by supplying a preset voltage to the sample side LEDs and varying that supplied to the reference LEDs until a zero calorimetric signal was obtained. The photodegradation of 2-NB was zero-order and varied in proportion to the input voltage supplied to the LED array. Analysis of the data (the rate of reaction was determined to be equal 1.04x10(-6)moldm(-3)s(-1) by pH titration) determined a reaction enthalpy of 5.0+/-0.6kJmol(-1). In the case of nifedipine, the LEDs in the array were operated individually in order to determine the causative wavelength of degradation. This was found to be 360nm, in agreement with the literature.

Development of an isothermal heat-conduction photocalorimeter.

Assessing photostability (particularly of pharmaceuticals) is of growing importance, but hampered by a lack of reliable, rapid experimental testing protocols and instrumentation. In particular, most approaches require irradiation of the sample separately from the analytical measurement, which increases both experimental complexity and the number of assumptions that must be made when calculating stability. One technique that may obviate this is photocalorimetry, principally because the reporter of change (heat) is measured directly as a sample is irradiated. Although not a new idea, the design challenges of photocalorimeters are complex, primarily because light power is being introduced to the calorimeter which can thus both saturate the amplifiers and swamp the response of the sample. Careful instrument design is thus paramount. The aim of this work was to develop a robust, compact, and easy to use photocalorimeter with the immediate focus of developing photostability assays for pharmaceuticals. The final instrument design, arrived at through a series of iterative design modifications, is based on a twin differential heat-conduction principle and achieves an average base line deflection of -0.04+/-0.11 microW with light irradiating the sample cell. The performance capabilities of the instrument were demonstrated using a model system; the photodegradation of 2-nitrobenzaldehyde in solution.