Use of isothermal heat conduction microcalorimetry to evaluate stability and excipient compatibility of a solid drug

Selzer, Torsten; Radau, Manfred; Kreuter, Jörg

doi:10.1016/s0378-5173(98)00177-x

Cited by 24 publications

(7 citation statements)

References 9 publications

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“…Some time ago we proposed 1-8 that isothermal heat conduction microcalorimetry could be used to determine both kinetic and thermodynamic parameters for reacting systems. These studies have subsequently been followed by those of Selzer et al. , (these latter papers have been followed by a commentary by one of us) . The advantages cited for the proposed procedure, which was applied mainly for the determination of the long-term stability of pharmaceutically related materials, were rapidity (only 50 h of observation is required, in principle, to discriminate between the first-order rate constants of 1 × 10 -11 and 2 × 10 -11 s -1 ), direct observation on the sample, whatever its form, nondestructive and noninvasive methods, and experimental simplicity.…”

Section: Introductionmentioning

confidence: 99%

Direct Determination of Equilibrium Thermodynamic and Kinetic Parameters from Isothermal Heat Conduction Microcalorimetry

et al. 2001

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Calorimetry is recognized − as a noninvasive, nondestructive method for the determination of both the thermodynamic and the kinetic parameters associated with chemical reactions. The most immediate applications of the technique have been found in the determination of long-term stability data particularly for pharmaceuticals. However, the methods proposed required that calorimetric data (thermal power, Φ, watts recorded as a function of time) be analyzed iteratively to obtain the order of the reaction n, the rate constant k, and the enthalpy change of reaction Δ R H. A necessary assumption in this process was that all of the sample placed into the calorimeter would react. This is obviously a severe constraint for the flexibility and application of the method. This paper reports a significant extension of the procedure that allows direct calculation of all of the above parameters. Moreover, the equations that are developed permit the determination of the actual quantity of the sample placed into the calorimeter that will react. Indeed, for successful determination of the desired kinetic, thermodynamic, and equilibrium parameters, it is not necessary, in principle, to have any knowledge about a sample other than its total mass. It is possible to determine, in addition to n, k, and Δ R H, the equilibrium constant K for the reaction studied together with the associated values of the Gibbs function and entropy changes Δ R G and Δ R S. Moreover, because the reaction is to be studied over a temperature range, the activation energy E a is also accessible.

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Section: Introductionmentioning

confidence: 99%

Direct Determination of Equilibrium Thermodynamic and Kinetic Parameters from Isothermal Heat Conduction Microcalorimetry

et al. 2001

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“…When the sample undergoes a thermal event, the difference in heat flow to a sample and to a reference is monitored against time or temperature while the temperature is programmed in a specific atmosphere [12]. Thus, chemical and physical processes are due to changes in free energy, and the decomposition of a drug is usually accompanied by an evolution of heat (exothermic process) [13].…”

Section: Introductionmentioning

confidence: 99%

Compatibility studies between piroxicam and pharmaceutical excipients used in solid dosage forms

et al. 2008

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Differential scanning calorimetry (DSC) with the support of Fourier transform infrared spectroscopy (FT-IR) was used as a screening technique for testing the compatibility of piroxicam (4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3carboxamide-1,1-dioxide) with various pharmaceutical excipients for solid dosage forms. Based on the results, magnesium stearate, stearic acid, and mannitol were found to show interaction with piroxicam. In conclusion, tools of DSC and FT-IR were successfully employed to evaluate the compatibility of piroxicam and selected excipients.

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“…Large exothermic heat responses were observed for mixtures of drug with MCC, potato starch and lactose, indicating these systems were unstable. A similar study has looked at the interactions of an active compressed into a tablet [69].…”

Section: Stability Assessment Of Api-excipient Mixturesmentioning

confidence: 96%

“…Interactions between a solid active and a range of excipients, including potato starch, α-lactose-monohydrate, microcrystalline cellulose (MCC) and talc have been investigated using IC, albeit between elevated temperatures of 60-80 o C [68]. Large exothermic heat responses were observed for mixtures of drug with MCC, potato starch and lactose, indicating these systems were unstable.…”

Section: Stability Assessment Of Api-excipient Mixturesmentioning

confidence: 99%

Stability Assessment of Pharmaceuticals and Biopharmaceuticals by Isothermal Calorimetry

Gaisford¹

2005

CPB

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The assessment of stability (of actives, excipients and/or formulated products) is an important, and often time-consuming, part of pharmaceutical product development. Conventionally, HPLC is used to quantify the concentrations of a parent compound and any degradation products as a function of storage time. HPLC, however, is relatively insensitive to small changes in concentration and it is often the case that stability assays are conducted under stress conditions, in order to accelerate any degradation processes. The Arrhenius relationship is then employed to give an initial prediction of stability under storage conditions while long-term studies, under storage conditions, are conducted to confirm these predictions. The properties of isothermal calorimetry, such as its intrinsic sensitivity to small changes in heat and invariance to the physical form of a sample, make it ideally suited for stability assessment because it obviates the need for an Arrhenius analysis. In addition, the ability to conduct titration or gas perfusion experiments vastly increases its range of applications. Recent advances in instrumental design and data analysis have made it easier to analyse data quantitatively for complex systems. It is the purpose of this review to highlight some of these developments, discuss them in the context of pharmaceutical and biopharmaceutical examples and explore some of the future challenges and applications of the technique.

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Use of isothermal heat conduction microcalorimetry to evaluate stability and excipient compatibility of a solid drug

Cited by 24 publications

References 9 publications

Direct Determination of Equilibrium Thermodynamic and Kinetic Parameters from Isothermal Heat Conduction Microcalorimetry

Direct Determination of Equilibrium Thermodynamic and Kinetic Parameters from Isothermal Heat Conduction Microcalorimetry

Compatibility studies between piroxicam and pharmaceutical excipients used in solid dosage forms

Stability Assessment of Pharmaceuticals and Biopharmaceuticals by Isothermal Calorimetry

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