Microcalorimetry, isothermal

Schmitt, E.A., Peck, K., Sun, Y., and Geoffroy, J-M., Rapid, practical and predictive excipient compatibility screening using isothermal microcalorimetry, Thermochim. Acta, 380, 175, 2001. 

Contact angle measurements Isothermal microcalorimetry Gravimetric sorption Inverse gas chromatography Differential scanning calorimetry Thermogravimetric analysis Isothermal microcalorimetry Infra red analysis X-ray diffraction... 

Isoproterenol, chemiluminescence, 647 (—)-Isopulegol, artemisinin synthesis, 277, 278 Isothermal microcalorimetry, oxidation stability evaluation, 672 Isotopomers... 

Table 2 Comparison of differential calorimetry and isothermal microcalorimetry (4)...

Willson (8) also studied the degradation of di-benzoyl peroxide using isothermal microcalorimetry. Literature values for the degradation of di-benzoyl peroxide at 100°C are 3.8 x 10 4 s 1 with an activation energy of... 

The interconversion of nitritopentamminecobalt (III) chloride to nitropentamminecobalt (III) chloride was also studied by Willson (8). Using isothermal microcalorimetry, estimates for the rate constant of interconversion and the thermodynamic reaction parameters were obtained directly, at 25°C, by fitting the data to the transformed Ng equation. The published... 

There are a number of excellent books that provide information on pharmaceutical thermal analysis but many do not include sections on isothermal microcalorimetry. Probably the most useful textbook in print is The Handbook of Thermal Analysis. Vol 1 Principles and practice, edited by ME Brown, Elsevier Science (Amsterdam), 1998, which comprehensively covers all aspects of thermal analysis. A more specialised, but now out of print, text is Biological Microcalorimetry, edited by AE Beezer, Academic Press (London), 1982 and an excellent chapter can be found in Principles of Thermal Analysis and Calorimetry, edited by PJ Haines, RSC (Cambridge), 2002. The subject of pharmaceutical uses of DSC is more widely covered with excellent texts including Biocalorimetry, edited by JE Ladbury and BZ Chowdhry, Wiley (Chichester), 1998 and Pharmaceutical Thermal Analysis, edited by JL Ford and P Timmins, Ellis Harwood, 1989 (although a new edition of this text is due, edited by JL Ford, P Timmins and G Buckton). 

Aso Y, Yoshioka S, Otsuka T, Kojima S. The physical stability of amorphous nifedipine determined by isothermal microcalorimetry. Chem Pharm Bull 1995 43(2) 300-303. 

Phipps MA, Winnike RA, Long ST, Viscomi F. Excipient compatibility assessment by isothermal microcalorimetry. J Pharm Pharmacol 1998 50(suppl) 9. 

Phipps MA, Mackin LA. Application of isothermal microcalorimetry in solid state drug development. PSTT 2000 3(1) 9 17. 

Experimental procedures for running excipient compatibility studies using isothermal microcalorimetry include the collection of power-time curves for each component of the mixture alone, as well as in combinations (Fig. 8). The separate drug and excipient curves can then be used to construct a theoretical non-interaction curve for the blend, which then is subtracted from the actual blend curves in order to define the interaction between the components. 

Phipps and Mackin (80) and Schmitt et al. (77) have advocated using isothermal microcalorimetry as a screening tool to assign relative risk and eliminate highly unstable excipients from subsequent model formulations. As seen in Table 11, Schmitt found that the results of an excipient screen with ABT-627 using isothermal microcalorimetry at 50°C qualitatively... 

Thermal property DSC, TGA Isothermal microcalorimetry Hot stage microscopy... 

The evolution in calorimetry technology has also led to the development of protocols for quantitative analysis (Buckton and Darcy 1999). Fiebich and Mutz (1999) determined the amorphous content of desferal using both isothermal microcalorimetry and water vapour sorption gravimetry with a level of detection of less than 1 per cent amorphous material. The heat capacity jump associated with the glass transition of amorphous materials MTDSC was used to quantify the amorphous content of a micronised drag substance with a limit of detection of 3 per cent w/w of amorphous... 

Figure 8 Structural relaxation times for quench-cooled glassy disaccharides as determined from enthalpy relaxation data. Structural relaxation times were obtained by a fit of the data to the stretched exponential function (see [37,50]). ( ) Data for sucrose obtained by differential scanning calorimetry on annealed samples [37], (O) Data for sucrose obtained by isothermal microcalorimetry [50]. (A) Data for trehalose obtained by isothermal microcalorimetry [50].

To fully understand the performance of amorphous materials, it is necessary to be able to measure the molecular mobility of the samples on interest. This is because at temperatures as far as 50 K below the glass transition temperature, pharmaceutical glasses exhibit significant molecular mobility that can contribute to both chemical and physical instability.The main techniques that have been developed for monitoring molecular motions in amorphous materials are nuclear magnetic resonance (NMR) and calorimetric techniques (e.g., DSC and isothermal microcalorimetry). Average molecular relaxation times and relaxation time distribution functions obtained from these... 

Interactions between water vapor and amorphous pharmaceutical solids were evaluated using isothermal microcalorimetry. " The desorption of water from theophylline monohydrate has been investigated using microcalorimetric approaches.The properties of surfactants and surface-active drugs in solution were studied by Attwood et al. " using calorimetry, while titration microcalorimetry has been utilized to elucidate the nature of specific interactions in several pharmaceutical polymer-surfactants systems. " Drug decomposition was evaluated as a function of different... 

Lehto, V.P. Salonen, J. Laine, E. Real time detection of photoreactivity in pharmaceutical solids and solutions with isothermal microcalorimetry. Pharm. Res. 1999, 16 (3), 368-373. 

Emas and Nyqist investigated the aging and stabilization of spray-congealed solid dispersions of carnauba wax. Isothermal microcalorimetry (IM) was... 

Sebhatu, T. Angberg, M. Ahlneck, C. Assessment of the degree of disorder in crystalline solids by isothermal microcalorimetry. Int. J. Pharm. 1994,104, 135-144. 

Gustafsson et al. used SSNMR and isothermal microcalorimetry to investigate the amorphous component of lactose. In general, the detection limits for crystalline forms are much better than for amorphous forms due to the much broader resonances characteristic of disordered systems. The two techniques were found to be in agreement with each other in the characterization of the degree of disorder in the system. Completely amorphous lactose (prepared by spray drying) was mixed with completely crystalline lactose monohydrate... 

Differential thermal analysis is applied and the appearance or disappearance of one or more peaks is noted. Isothermal microcalorimetry can also be employed as well as a thermal activity monitor (TAM) technique. 

For such compatibility studies, isothermal microcalorimetry has been suggested (e.g., Ref. ). 

Buckton, G. Apphcation of isothermal microcalorimetry in the pharmaceutical sciences. Thermochim. Acta 1995, 248, 117-129. 

Humera, A. Buckton, G. Rawlins, D.A. The use of isothermal microcalorimetry in the study of small degrees of amorphous contend of hydrophobic powder. Int. J. Pharm. 1996,130, I95-20I. 

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