Microcalorimetry Techniques Research Articles

Immersion Calorimetry for the Characterization of PD Catalysts Supported on Activated Carbon

Activated carbons obtained from coconut peel were oxidized using hydrogen peroxide. Superficial characteristics of these carbons were determined through N2 and CO2 isotherms and functional groups were characterized by TPD. Finally, the microcalorimetry technique was used in order to obtain the immersion enthalpies in diverse liquids and established the relation between them and the results obtained by the other characterization techniques. The results suggested that the immersion calorimetry allow establishing the difference between the supports and the catalysts.

Hydroisomerization of model FCC naphtha over sulfided Co(Ni)–Mo(W)/MCM-41 catalysts

Deep hydrodesulfurization (HDS) of gasoline generally brings about the saturation of olefins and leads to the serious octane number losses. Conversion of linear olefins to branched ones followed by hydrogenation to isoalkanes would minimize such octane number losses. In this work, MCM-41-supported Co–Mo, Ni–Mo and Ni–W catalysts were prepared by the incipient wetness impregnation method, and compared with an industrial Co–Mo/γ-Al 2O 3 catalyst. The surface acidities were measured by the techniques of microcalorimetry and infrared spectroscopy for the adsorption of ammonia, and probed by the reaction of conversion of isopropanol. The isomerization and hydrogenation of 1-hexene as well as the HDS of thiophene were studied by using model FCC naphtha. It was found that the sulfidation enhanced significantly the surface Brønsted acidity that favored the skeletal isomerization of 1-hexene under the HDS conditions. Since the isomerization and hydrogenation of 1-hexene are the two competition reactions, the catalysts with relatively lower hydrogenation activity may have higher selectivity to the isomerization reactions. The Co–Mo/MCM-41 showed the high selectivity to the skeletal isomerization reactions due to its strong surface Brønsted acidity and the relatively low hydrogenation activity. On the other hand, the Ni–Mo/MCM-41 exhibited high hydrogenation activity and therefore low selectivity to the isomerization reactions although it possessed quite strong surface Brønsted acidity. The Ni–W/MCM-41 exhibited the low activity for the HDS of thiophene and isomerization of 1-hexene due to the poor dispersion of active metals.

Postradiation polymerization of tetrafluoroethylene on mineral supports at low temperatures

The low-temperature graft polymerization of tetrafluoroethylene (TFE) on mineral supports (SiO2, Al2O3, TiO2, and activated charcoal) has been investigated by the microcalorimetry, ESR, and IR spectroscopy techniques. It has been shown that polymerization of TFE is initiated by radical ion centers formed upon radiolysis of the support. The initiation stage includes the interaction of a radical ion particle of the support with a monomer molecule yielding a growing neutral radical. The radical growth of polymer chains has been confirmed by the appearnce of the ESR spectrum of terminal fluoroalkyl radicals ∼CF2−CF2, and the covalent C-Si bonds of the polymer with the support have been detected by means of IR spectroscopy. The efficiency of the low-temperature graft polymerization depends on the monomer sorption and the sorbent nature: the highest efficiency is observed for Al2O3 and, then, macroporous glasses; grafting proceeds to the least extent (yield below 5%) on the carbon supports, which do not the form radical ion centers during radiation activation.

Investigation of the Impact of Annealing on Global Molecular Mobility in Glasses: Optimization for Stabilization of Amorphous Pharmaceuticals

The purpose of this research was to investigate the effect of annealing on the molecular mobility in lyophilized glasses using differential scanning calorimetry (DSC) and isothermal microcalorimetry (IMC) techniques. A second objective that emerged was a systematic study of the unusual pre-T(g) thermal events that were observed during DSC warming scans after annealing. Aspartame lyophilized with three different excipients; sucrose, trehalose and poly vinyl pyrrolidone (PVP) was studied. The aim of this work was to quantify the decrease in mobility in amorphous lyophilized aspartame formulations upon systematic postlyophilization annealing. DSC scans of aspartame:sucrose formulation (T(g) = 73 degrees C) showed the presence of a pre-T(g) endotherm which disappeared upon annealing. Aspartame:trehalose (T(g) = 112 degrees C) and aspartame:PVP (T(g) = 100 degrees C) showed a broad exotherm before T(g) and annealing caused appearance of endothermic peaks before T(g). This work also employed IMC to measure the global molecular mobility represented by structural relaxation time (tau(beta)) in both un-annealed and annealed formulations. The effect of annealing on the enthalpy relaxation of lyophilized glasses, as measured by DSC and IMC, was consistent with the behavior predicted using the Tool-Narayanaswamy-Moynihan (TNM) phenomenology (Luthra et al., 2007, in press). The results show that the systems annealed at T(g) -15 degrees C to T(g) -20 degrees C have the lowest molecular mobility.

Phase Equilibria Study in Binary Systems (Tetra-n-butylphosphonium Tosylate Ionic Liquid + 1-Alcohol, or Benzene, or n-Alkylbenzene)

Ambient pressure (solid + liquid) equilibria (SLE) and (liquid + liquid) equilibria (LLE) of binary systems--ionic liquid (IL) tetra- n-butylphosphonium p-toluenesulfonate + 1-alcohol (1-butanol, 1-hexanol, 1-octanol, 1-decanol, or 1-dodecanol), benzene, or n-alkylbenzene (toluene, ethylbenzene, n-propylbenzene)-have been determined by using dynamic method in a broad range of mole fractions and temperatures from 250 to 335 K. For binaries containing alcohol, simple eutectic diagrams were observed with complete miscibility in the liquid phase. Only in the case of system [IL + n-propylbenzene] was mutual immiscibility with an upper critical solution temperature (UCST) with low solubility of the IL in the alcohol and high solubility of the alcohol in the IL detected. The basic thermal properties of pure IL, i.e., melting and glass-transition temperatures as well as enthalpy of melting, have been measured with differential scanning microcalorimetry technique (DSC). Well-known UNIQUAC, Wilson, NRTL, NRTL1, and NRTL2 equations have been fitted to obtain experimental data sets. For the system containing immiscibility gap [IL + n-propylbenzene], parameters of the equations have been derived only from SLE data. As a measure of goodness of correlations, root-mean square deviations of temperature have been used. These experimental results were compared to the previously measured binary systems with tetra- n-butylphosphonium methanesulfonate. Changing anion from methanesulfonate to p-toluenesulfonate decreases solubilities in systems with alcohols and increases the solubilities in binary systems with benzene and alkylbenzenes.

Physicochemical Studies on the Interaction of Gelatin with Cationic Surfactants Alkyltrimethylammonium Bromides (ATABs) with Special Focus on the Behavior of the Hexadecyl Homologue

The interaction of a denatured interfacially active protein, gelatin (G) (at pH 9, above its isoelectric pH 4.84, and ionic strength mu=0.005), with a cationic amphiphile, hexadecyl (or cetyl) trimethylammonium bromide, CTAB, has been elaborately studied using a variety of techniques. Two types of protein-surfactant complexes at a concentration below the normal critical micellar concentration (cmc) were formed in solution. The first, G-CTAB (monomer) combined complex (GS(n)(I)) adsorbed at the air/solution interface, followed by its gradual transformation to the poor interfacially active second G-CTAB (aggregate) complex (GS(m)(B)) at a critical aggregation concentration (cac) of the interacting oppositely charged surfactant. In the higher concentration range, upon completion of GS(m)(B) formation, coacervation (association of GS(m)(B)) led to add turbidity. With increasing addition of CTAB, the coacervates became disintegrated and ultimately remained dissolved in the free micellar solution of CTAB. The above features were studied using the techniques of tensiometry, conductometry, turbidimetry, fluorimetry, and microcalorimetry. The interaction features were prominent at [G] >or= 0.05 g %, and several of these were either marginal or absent at [G]<0.05 g %. The denatured protein was found to form viscous as well as gel-forming consistencies at higher [G] and at lower temperature. A temperature variation study on the interaction of G with CTAB has revealed that enhanced interaction takes place at higher temperature. The effect of [G] on its interaction with cationic surfactants of varying chain length in the alkyltrimethylammonium bromide (ATAB) series has been also studied; a similar interactional profile as that of CTAB has been exhibited by octadecyltrimethylammonium bromide; however, the lower homologues (dodecyl- and tetradecyl-) of ATAB have offered different profiles. It has been found that the ATABs with higher alkyl chain lengths were more interactive with negatively charged G than their lower homologues. Quantification of the results in terms of different transition points, counterion binding of the protein-bound surfactant aggregates and free micelles, the enthalpy of binding interactions and energetics of ATAB micellization, and so forth have been studied. The results have been rationalized in terms of an interaction model.

Influence of cultivation conditions on spatial structure and functional activity of OmpF-like porin from outer membrane of Yersinia pseudotuberculosis

The influence of cultivation conditions of pseudotuberculosis bacteria on the spatial structure and the functional activity of nonspecific OmpF-like porin was studied by means of optical spectroscopy, scanning microcalorimetry, and bilayer lipid membrane technique. With this goal, porin samples isolated from microbial masses grown at different temperatures, nutrient medium densities, and growth phases were characterized. According to CD data, the porin samples under investigation represent beta-sheet proteins. It was found that the protein isolated from the colonial culture of pseudotuberculosis bacteria grown at low temperature has the most compact structure. Using intrinsic protein fluorescence, it was shown that different conditions of pseudotuberculosis bacteria cultivation (temperature, medium, growth phase) led to the changes in spectral properties of porin fluorescence due to the redistribution of the contributions of tyrosine and different classes of tryptophan residues to the total protein emission. Heat inactivation of porin samples was studied using CD spectroscopy, intrinsic protein fluorescence, and scanning microcalorimetry. Spatial features of the porin samples were found to affect their functional activities. Considering all these data, it is possible to correlate the spatial structure and functional activity of porin samples isolated under different cultivation conditions of bacteria and the composition of the outer membrane lipid matrix.

Standard molar enthalpies of formation of the three isomers of chloroanisole

The standard ( p ∘ = 0.1 MPa) molar enthalpies of formation, in the liquid phase, of 2-, 3- and 4-chloroanisoles, at T = 298.15 K, were derived from their standard massic energies of combustion, in oxygen, to yield CO 2(g) and HCl · 600H 2O(l), measured by rotating bomb combustion calorimetry. The Calvet high-temperature microcalorimetry technique was used to measure the standard molar enthalpies of vaporization of these compounds. - Δ c U m ∘ ( l ) / ( kJ · mol - 1 ) - Δ f H m ∘ ( l ) / ( kJ · mol - 1 ) Δ l g H m ∘ / ( kJ · mol - 1 ) 2-Chloroanisole 3622.0 ± 1.6 154.1 ± 1.8 55.0 ± 0.8 3-Chloroanisole 3615.9 ± 1.6 160.2 ± 1.8 53.6 ± 0.8 4-Chloroanisole 3619.2 ± 1.5 156.9 ± 1.8 54.8 ± 0.8 From these two sets of experimental values, the standard molar enthalpies of formation in the gaseous phase, at T = 298.15 K, were derived, compared with the same parameters estimated by the Cox scheme and interpreted in terms of molecular structure.

Structural, acidic and redox properties of V2O5-TiO2-SO42− catalysts

Abstract A series of V2O5-TiO2 (VT) catalysts with V2O5 contents from 15 to 75 wt% were prepared by the co-precipitation method and doped with SO42− ions. The structural properties were characterized by X-ray diffraction (XRD), Raman spectroscopy (LRS) and X-ray photoelectron spectroscopy (XPS). The surface acidity was determined by the techniques of NH3 adsorption microcalorimetry and pyridine adsorption infrared spectroscopy (FT-IR). Isopropanol (IPA) and methanol probe reactions in the presence of O2 were employed to provide the information about surface acidity and redox properties simultaneously. The results from XRD and LRS showed that V2O5 was well dispersed on the surface of TiO2 when the vanadia content was below 25 wt%. XPS showed that both vanadium and titanium were present in their fully oxidized states in all the samples. The SO42− doped VT samples had the sulfur oxidation state of +6. The results of NH3 adsorption microcalorimetry and pyridine adsorption FT-IR indicated that the VT catalysts possessed identical surface acid densities independently of the V2O5 content, and that both Bronsted and Lewis acid sites were present on their surfaces. The results of isopropanol probe and methanol oxidation reactions suggested that the surface acidity of VT catalysts was improved upon SO42− doping, as evidenced by the simultaneous decrease in the amounts of oxidation products and increase in the amounts of dehydration products. A high selectivity of 90% to dimethoxymethane (DMM) was measured on the SO42− modified 25%V2O5-75%TiO2 catalyst, with 54% conversion of methanol at 413 K.

Effects of pH on structural and functional properties of porin from the outer membrane of Yersinia pseudotuberculosis. I. Functionally important conformational transitions of yersinin

The changes in the structural and functional properties of yersinin, a porin from the outer membrane of Yersinia pseudotuberculosis, were studied in the pH range 8.0–2.0 using SDs-PAGE, scanning microcalorimetry, optical spectroscopy and bilayer lipid membrane technique. It was found that in the pH range under study the changes in the spatial structure of yersinin were biphasic. In the first steps of pH titration (pH 8.0–4.5), porin underwent a series of conformational transitions, which did not affect the trimeric structure of its molecule. In the second step (pH 4.0–2.0), structural rearrangements led to dissociation of the protein trimers into monomers. It is noteworthy that complete unfolding of the polypeptide chain of the protein was not observed even at low values of pH. Thus, at pH 2.0 the conformational intermediate of the protein retained up to 50% of its regular secondary structure. Studies of current fluctuations in the bilayer lipid membrane revealed that in weakly acidic media the conductivity of yersinin pores was decreased by one order of magnitude. The most drastic changes in the conductivity of the model membrane were observed at pH 5.8, whereas a further decrease of pH to 5.0 resulted in the closure of porin channels. It was concluded that the observed changes in the pore-forming properties of yersinin in a narrow range of pH represent an early step in the adaptation of bacteria to the changing conditions of the environment and entail control over the biosynthesis of nonspecific porins. The pH-dependent changes in the structure and pore-forming properties of yersinin provide additional evidence in favor of conformational and functional plasticity of porins.

Structural, acidic and redox properties of V2O5/NbP catalysts

V2O5 supported on niobium phosphate (NbP) with V2O5 loadings from 5 to 25 wt% were investigated by using different techniques. The structural properties were characterized by O2 chemisorption, X-ray diffraction (XRD), Raman spectroscopy (LRS) and X-ray photoelectron spectroscopy (XPS). The surface acidity was determined by the techniques of microcalorimetry and infrared spectroscopy (FTIR) using NH3 as a probe molecule. Isopropanol (IPA) and methanol probe reactions in the presence of O2 were employed to provide the information about the surface acidity and redox property simultaneously. V2O5 is well dispersed on the surface of NbP according to the results from XRD and LRS with a V2O5 loading lower than 15 wt%. The vanadium and niobium elements in V2O5/NbP catalysts were present in the +5 oxidization state as observed from XPS. Chemical adsorption of O2 showed that vanadia dispersed on NbP with about 60% dispersion. The results from NH3 adsorption microcalorimetry suggested that the loaded V2O5 weakened the surface acidity of NbP while increased the proportion of weak acid sites. The results from IPA conversion reaction pointed out that IPA only converted to dehydration products (propylene (PPE) and diisopropyl ether (DIPE)) on NbP. The addition of V2O5 on NbP led to an oxidative product acetone (ACE), but not as much as on bulk V2O5. These results indicated that NbP possessed only surface acidity and weakened the redox property of supported V2O5. Accordingly, NbP produced only dimethyl ether (DME) from the dehydration of methanol owing to the lack of redox property, while the V2O5/NbP catalysts produced mainly dimethoxymethane (DMM) due to its acidic-redox bi-functional character. Specifically, methanol was first oxidized on the redox sites of V2O5/NbP to produce formaldehyde (FA) which was then condensed with additional methanol on the acidic sites of V2O5/NbP to form DMM.

Aging and intermittency in ap-spin model of a glass

We numerically analyze the statistics of the heat flow between an aging system and its thermal bath, following a method proposed and tested for a spin-glass model in a recent paper [P. Sibani and H. J. Jensen, Europhys. Lett. 69, 563 (2005)]. The present system, which lacks quenched randomness, consists of Ising spins located on a cubic lattice, with each plaquette contributing to the total energy the product of the four spins located at its corners. Similarly to our previous findings, energy leaves the system in rare but large, so-called intermittent, bursts which are embedded in reversible and equilibriumlike fluctuations of zero average. The intermittent bursts, or quakes, dissipate the excess energy trapped in the initial state at a rate which falls off with the inverse of the age. This strongly heterogeneous dynamical picture is explained using the idea that quakes are triggered by energy fluctuations of record size, which occur independently within a number of thermalized domains. From the temperature dependence of the width of the reversible heat fluctuations we surmise that these domains have an exponential density of states. Finally, we show that the heat flow consists of a temperature independent term and a term with an Arrhenius temperature dependence. Microscopic dynamical and structural information can thus be extracted from numerical intermittency data. This type of analysis seems now within the reach of time resolved microcalorimetry techniques.

Rapid Assessment of the Structural Relaxation Behavior of Amorphous Pharmaceutical Solids: Effect of Residual Water on Molecular Mobility

Use RH-perfusion microcalorimetry and other analytical techniques to measure the interactions between water vapor and amorphous pharmaceutical solids; use these measurements and a mathematical model to provide a mechanistic understanding of observed calorimetric events. Isothermal microcalorimetry was used to characterize interactions of water vapor with a model amorphous system, spray-dried raffinose. Differential scanning calorimetry was used to measure glass transition temperature, T (g). High-sensitivity differential scanning calorimetry was used to measure enthalpy relaxation. X-ray powder diffraction (XRPD) was used to confirm that the spray-dried samples were amorphous. Scanning electron microscopy (SEM) was used to examine particle morphology. Gravimetric vapor sorption was used to measure moisture sorption isotherms. Thermogravimetric analysis (TGA) was used to measure loss on drying. A moisture-induced thermal activity trace (MITAT) provides a rapid measure of the dependence of molecular mobility on moisture content at a given storage temperature. At some relative humidity threshold, RH(m), the MITAT exhibits a dramatic increase in the calorimetric rate of heat flux. Simulations using calorimetric data indicate that this thermal event is a consequence of enthalpy relaxation. RH-perfusion microcalorimetry is a useful tool to determine the onset of moisture-induced physical instability of glassy pharmaceuticals and could find a broad application to determine appropriate storage conditions to ensure long-term physical stability. Remarkably, thermal events measured on practical laboratory timescales (hours to days) are relevant to the stability of amorphous materials on much longer, pharmaceutically relevant timescales (years). The mechanistic understanding of these observations in terms of enthalpy relaxation has added further value to the use of RH-perfusion calorimetry as a rapid means to characterize the molecular mobility of amorphous solids.

An investigation of strontium nitrite and its role in the ageing of the magnesium–strontium nitrate pyrotechnic system using isothermal microcalorimetry and thermal analysis techniques

A sample of strontium nitrite has been synthesised and thermally characterised to investigate its role in the ageing of magnesium–strontium nitrate pyrotechnic compositions in the presence of water vapour. Studies by isothermal microcalorimetry show that the addition of strontium nitrite to a 50% magnesium–50% strontium nitrate composition eliminated the induction reaction normally observed in closed ampoule studies in air at 50 °C and relative humidities in the range 65–69%.

Functional properties of whey proteins as affected by dynamic high-pressure treatment

An ultra high-pressure homogenizer was used to treat whey protein isolate solutions (3%, w/w). The treated solutions (up to 300 MPa) were characterised for both physico-chemical properties (particle size distribution, surface hydrophobicity and structural conformation) and functional properties (solubility, foaming stability and interfacial rheology). Dynamic high-pressure treatment did not affect the conformation of the proteins (determined by micro-calorimetry, size-exclusion chromatography and electrophoretic technique). This treatment dissociated large protein aggregates leading to unmasking of the buried hydrophobic groups without affecting protein solubility. Interactions may then occur between these groups that enhance the viscoelasticity of air-water interfaces (assessed by drop tensiometry) and improve foam stability (evaluated by sparging method). Dynamic high-pressure-treated whey proteins showed better foaming and stabilising properties.

Comparative study on the gas-phase adsorption of hexane over zeolites by calorimetry and inverse gas chromatography

The scope of this work is to carry out a systematic comparison of inverse gas chromatography (IGC) and microcalorimetry as tools for the study of the gas-phase adsorption of organic vapours (using hexane as model compound) on zeolitic materials (using different Mn, Co and Fe-exchanged NaX and CaA zeolites). Adsorption isotherms were recorded using both techniques in the temperature range of 150–250 °C, being observed that the shape of the isotherms obtained with the dynamic (IGC) and static (microcalorimetry) techniques was surprisingly similar in the pressure range at which both techniques are applicable (low surface coverages). Concerning to the measurement of the strength of the adsorption, calorimetric data provide two parameters related to the adsorption enthalpy: the initial differential heat and the isosteric adsorption enthalpy. A great coincidence was found between the last one and the adsorption enthalpy determined by IGC (4–20% of difference, depending on the studied material). The behaviour of the initial differential heat depends strongly on the studied material, being in some cases closely related to the other two parameters and temperature-independent (in the case on Mn-exchanged zeolites), whereas for the Co-CaA and Fe-CaA zeolites, it is temperature-dependent, being not correlated with the other parameters in this case. The main conclusion of this work is that IGC is an attractive alternative to the static microcalorimetric data for obtaining information on the adsorption of organic compounds on microporous materials.

Adsorption of Non Polar and Quadrupolar Gases in Siliceous Faujasite: Molecular Simulations and Experiments

The adsorption of non polar (argon, methane) and quadrupolar (carbon dioxide, nitrogen) gases on siliceous Faujasite at ambient temperature and high pressure conditions up to 50 bar, is investigated both experimentally and theoretically by combining Microcalorimetry and Grand Canonical Monte Carlo techniques. The aim of this present work is to evaluate the adsorption isotherms as well as the evolution of the differential enthalpies of adsorption as a function of coverage, for each of the gases under study, and to compare directly results of simulations with our own experimental data. To this purpose, the choice of reliable interatomic potentials required to describe both the adsorbate/framework and adsorbate/adsorbate interactions is crucial. This work is thus based on new transferable pair potential models for methane and carbon dioxide, recently developed by one of the authors using quantum mechanical methods. Finally, we propose a simplified model which can relate the differential enthalpy of adsorption at low coverage to the polarisability of the gases.

A study of the influence of the fuel to oxidant ratio on the ageing of magnesium–strontium nitrate pyrotechnic compositions using isothermal microcalorimetry and thermal analysis techniques

The influence of the fuel to oxidant ratio on the ageing behaviour of the magnesium–strontium nitrate pyrotechnic system in the presence of water vapour has been investigated by isothermal microcalorimetry in conjunction with chemical and thermal analysis measurements. The major products of ageing were identified as magnesium hydroxide and strontium nitrite. Measurement of the ratio of the amount of magnesium hydroxide formed to that of strontium nitrate reacted has shown that for compositions containing from 10 to 60% magnesium, a major component of the ageing process could be represented by the equation 3Mg + Sr(NO 3) 2 + 4H 2O → 3Mg(OH) 2 + Sr(NO 2) 2 + H 2. DSC studies have confirmed that the formation of strontium nitrite during ageing has a significant influence on the high temperature pyrotechnic reaction between magnesium and strontium nitrate.

Surface study of graphite-supported Ru–Co and Ru–Ni bimetallic catalysts

Several graphite-supported Ru–Co and Ru–Ni bimetallic catalysts were comparatively studied by X-ray diffraction (XRD) and CO adsorption microcalorimetry. The correlation of the results thus obtained from these techniques with those on the n-butane hydrogenolysis reaction test, provides useful information about the type and distribution of the surface active sites. The CO adsorption microcalorimetry technique provides, in some cases, information that allows identification and quantification of the surface sites of the metallic nanoparticles. Thus, these data may be used to identify specific catalytic properties (activity and selectivity) in the n-butane/hydrogen test, and how such properties are modified on the different surface sites. Also, comparison with the parent monometallic catalysts allows to envisage the contribution of each individual metal to the total surface composition or else of the formation of alloys or bimetallic surface clusters. The results so obtained suggest the formation of surface Ru–Co and Ru–Ni alloys on these bimetallic catalysts, their contribution to the surface composition depending on the relative atomic ratio (Ru/M) and on the pre-treatment (reduction) conditions.

Use of isothermal microcalorimetry in pharmaceutical preformulation studies, Part I. Monitoring crystalline phase transitions

Solid-state transformation kinetics of two crystal forms of a synthetic tetrapeptide was monitored by isothermal microcalorimetry and complementary solid-state analytical techniques. Form B, the crystal form obtained from the synthetic process transformed to Form D upon exposure to higher relative humidity conditions (>60% RH). The transformation occurred rapidly at higher temperature, and relative humidities. An intermediate phase of very low crystallinity (amorphous-like phase) was observed when transformation was slow. Form D was observed to be physically stable at higher relative humidities and thus the preferred crystal form for development. Exposure of Form B to high relative humidity was the only process through which Form D was obtained. Optimal conditions for transformation of Form B to Form D were determined by microcalorimetric experiments and were used for larger scale processing of Form B to Form D.