Quantitative Analysis of Solid-State Processes Studied With Isothermal Microcalorimetry

Abstract

Quantitative analysis of solid-state processes from isothermal microcalorimetric data is straightforward if data for the total process have been recorded and problematic (in the more likely case) when they have not. Data are usually plotted as a function of fraction reacted (α); for calorimetric data, this requires knowledge of the total heat change (Q) upon completion of the process. Determination of Q is difficult in cases where the process is fast (initial data missing) or slow (final data missing). Here we introduce several mathematical methods that allow the direct calculation of Q by selection of data points when only partial data are present, based on analysis with the Pérez-Maqueda model. All methods in addition allow direct determination of the reaction mechanism descriptors m and n and from this the rate constant, k. The validity of the methods is tested with the use of simulated calorimetric data, and we introduce a graphical method for generating solid-state power-time data. The methods are then applied to the crystallization of indomethacin from a glass. All methods correctly recovered the total reaction enthalpy (16.6 J) and suggested that the crystallization followed an Avrami model. The rate constants for crystallization were determined to be 3.98 × 10(-6), 4.13 × 10(-6), and 3.98 × 10(-6) s(-1) with methods 1, 2, and 3, respectively.

Structural Characterization of Amorphous Solid Dispersions

“…Originally derived for a homogeneous single component system, zero or constant nucleation rate in course of crystallization assumed by JMAK model can be an oversimplification of nucleation process for the process starting from ASD. Furthermore, this model is advocated to be inefficient in explaining crystal impingement at higher α C (> 0.8; Sousa et al 2010). The JMAK model is occasionally modified to account for the decrease in nucleation rate accompanied by the increase in the growth rate while crystallization progresses.…”

“…The integration of the heat flow curve (power data) over a particular time interval provides heat (q). Provided the total enthalpy of a process (Q) is known, the temporal calorimetric data generates a solid-state kinetics in the form of a fraction converted (α = q/Q; Sousa et al 2010).…”

“…There are always chances to miss earlier induction points for rapidly crystallizing APIs especially in the absence of a crystallization inhibitor or while measuring at elevated RH. Sousa et al (2010) estimated the total heat of crystallization by applying mathematical models on intermediate experimental IMC data points and found that the methods correctly predicted the heat of crystallization, in case of amorphous indomethacin. Thus, such models can enable the calculation of the total heat for missing data points of a very fast or slow process.…”

Thermally decarboxylated sodium bicarbonate: Interactions with water vapour, calorimetric study

“…Isothermal calorimetry (ITC) is one of the most useful methods to study physical changes occurring between pharmaceutical components [12] , [13] , [14] , [15] . In our previous study on pyrolytically decarboxylated NaHCO 3 [16] only a narrow range of decarboxylation degrees was investigated by ITC at two humidities: 54% and 100% RH.…”

Searching for the main anti‐bacterial components in artificial Calculus bovis using UPLC and microcalorimetry coupled with multi‐linear regression analysis

“…As an efficient, noninvasive and versatile method for measuring the heat production in many fields, microcalorimetry can be applied to reflect various reaction processes of physics, chemistry, life science and environmental science [23,24]. Recently it has been successfully used to evaluate the anti-bacterial abilities of some components in CHM [25].…”