Search

Solid-state methods for cooling and heating promise a sustainable alternative to current compression cycles of greenhouse gases and inefficient fuel-burning heaters. Barocaloric effects (BCE) driven by hydrostatic pressure (p) are especially encouraging in terms of large adiabatic temperature changes (|¿T| ˜¿10 K) and isothermal entropy changes (|¿S| ˜¿100 J K-1 kg-1). However, BCE typically require large pressure shifts due to irreversibility issues, and sizeable |¿T| and |¿S| seldom are realized in a same material. Here, the existence of colossal and reversible BCE in LiCB11H12 is demonstrated near its order-disorder phase transition at ˜380 K. Specifically, for ¿p ˜ 0.23 (0.10) GPa, |¿Srev| = 280 (200) J K-1 kg-1 and |¿Trev| = 32 (10) K are measured, which individually rival with state-of-the-art BCE figures. Furthermore, pressure shifts of the order of 0.1 GPa yield huge reversible barocaloric strengths of ˜2 J K-1 kg-1 MPa-1. Molecular dynamics simulations are performed to quantify the role of lattice vibrations, molecular reorientations, and ion diffusion on the disclosed BCE. Interestingly, lattice vibrations are found to contribute the most to |¿S| while the diffusion of lithium ions, despite adding up only slightly to the entropy change, is crucial in enabling the molecular order–disorder phase transition., Postprint (published version)

Materials undergoing pressure-driven solid–solid phase transformations can be a valuable alternative for eco-friendly refrigeration, heat pumping and waste heat recovery based on the barocaloric effect. Ferroelectric compounds and plastic crystals have shown their potential in these fields because they may undergo large changes in volume and entropy at the transition, which underpin a large pressure-induced caloric response. Recently, a new class of materials combining a high-temperature plastic phase with a low-temperature ferroelectric phase has been reported. Here we investigate the barocaloric properties of two such “ferroelectric plastic crystals”, namely quinuclidinium perrhenate (C7H14NReO4) and tetramethylammonium tetrachloroferrate (N(CH3)4[FeCl4]). The reversible adiabatic temperature changes under pressure of around 100 MPa (8 K for C7H14NReO4 and 21 K for N(CH3)4[FeCl4]) reach values comparable to other plastic crystals and other materials, which demonstrates a good prospect for this novel barocaloric materials family. The dynamics of the plastic phase for C7H14NReO4 has been investigated by means of quasielastic neutron scattering., Peer Reviewed, Postprint (author's final draft)

For over a century, it was thought that the crystalline polymorph II of benzophenone does not possess a stable domain in the pressure–temperature phase diagram. With a combination of new experimental results and literature data, this case of crystalline dimorphism has finally been solved and it is shown that form II possesses a stable domain at high pressure and high temperature, even though its density is lower than that of form I, the stable form under ordinary pressure and temperature conditions. The phase diagram of benzophenone is a clear demonstration of the fact that to understand the phase behaviour of a chemical substance both the exchange of heat (due to the change in intermolecular interactions) and work (due to the change of volume at a given pressure) need to be taken into account., Postprint (published version)

Van der Waals chalcogenides and chalcohalides have the potential to become the next thin film PV breakthrough, owing to the earth-abundancy and non-toxicity of their components, and their stability, high absorption coefficient and quasi-1D structure, which leads to enhanced electrical anisotropic properties when the material is oriented in a specific crystalline direction. However, quasi-1D semiconductors beyond Sb2(S,Se)3, such as SbSeX chalcohalides, have been scarcely investigated for energy generation applications, and rarely synthesised by physical vapor deposition methodologies, despite holding the promise of widening the bandgap range (opening the door to tandem or semi-transparent devices), and showing enticing new properties such as ferroelectric behaviour and defect-tolerant nature. In this work, SbSeI and SbSeBr micro-columnar solar cells have been obtained for the first time by an innovative methodology based on the selective halogenation of Sb2Se3 thin films at pressure above 1 atm. It is shown that by increasing the annealing temperature and pressure, the height and density of the micro-columnar structures grows monotonically, resulting in SbSeI single-crystal columns up to 30 µm, and tuneable morphology. In addition, solar cell prototypes with substrate configuration have shown remarkable Voc values above 550 mV and 1.8 eV bandgap., Peer Reviewed, Postprint (published version)

Plastic crystals have emerged as benchmark barocaloric (BC) materials for potential solid-state cooling and heating applications due to huge isothermal entropy changes and adiabatic temperature changes driven by pressure. In this work we investigate the BC response of the neopentane derivative 2-methyl-2-nitro-1-propanol (NO2C(CH3)2CH2OH) in a wide temperature range using x-ray diffraction, dilatometry and pressure-dependent differential thermal analysis. Near the ordered-to-plastic transition, we find colossal BC effects of $\simeq$400¿J¿K-1¿kg-1 and $\simeq$5¿K upon pressure changes of 100¿MPa. Although reversible effects at the transition are obtained only from higher pressure changes due to hysteretic effects, we do obtain fully reversible BC effects from any pressure change in individual phases, that become giant at moderate pressures due to very large thermal expansion, especially in the plastic phase. From our measurements, we also determine the crystal structure of the low-temperature phase and estimate the contribution of the configurational disorder and the volume change to the total transition entropy change., Peer Reviewed, Postprint (author's final draft)

The magnetically frustrated manganese nitride antiperovskite family displays significant changes of entropy under changes in hydrostatic pressure near a first-order antiferromagnetic to paramagnetic phase transition that can be useful for the emerging field of solid-state barocaloric cooling. In previous studies, the transition hysteresis has significantly reduced the reversible barocaloric effects (BCE). Here we show that the transition hysteresis can be tailored through quaternary alloying in the Mn3Cu$_{1-x}$Sn$_{x}$N system. We find the magnitude of hysteresis is minimised when Cu and Sn are equiatomic (x¿=¿0.5) reaching values far less than previously found for Mn3AN ($A = $ Pd, Ni, Ga, Zn), whilst retaining entropy changes of the same order of magnitude. These results demonstrate that reversible BCE are achievable for p¿<¿100 MPa in the Mn3(A, B)N family and suggest routes to modify the transition properties in compounds of the same family., Peer Reviewed, Postprint (published version)

The availability of sufficient amounts of form I of benzocaine has led to the investigation of its phase relationships with the other two existing forms, II and III, using adiabatic calorimetry, powder X-ray diffraction, and high-pressure differential thermal analysis. The latter two forms were known to have an enantiotropic phase relationship in which form III is stable at low-temperatures and high-pressures, while form II is stable at room temperature with respect to form III. Using adiabatic calorimetry data, it can be concluded, that form I is the stable low-temperature, high-pressure form, which also happens to be the most stable form at room temperature; however, due to its persistence at room temperature, form II is still the most convenient polymorph to use in formulations. Form III presents a case of overall monotropy and does not possess any stability domain in the pressure–temperature phase diagram. Heat capacity data for benzocaine have been obtained by adiabatic calorimetry from 11 K to 369 K above its melting point, which can be used to compare to results from in silico crystal structure prediction., Peer Reviewed, Postprint (published version)

The dimorphism of the corticosteroid anti-inflammatory drug prednisolone has been investigated by the construction of a topological pressure–temperature phase diagram, using crystallographic and calorimetric data. The system is enantiotropic, because the temperature of the I-II equilibrium under atmospheric conditions (400–463 K) is lower than that of the two melting equilibria (518.7 K for form II and 526.3 K for form I). The slope of the I-II equilibrium in the pressure–temperature phase diagram is negative and relatively steep; therefore, form II, which is the stable form at room temperature, will not easily encounter conditions where form I will become stable even under industrial processing conditions. On the other hand, extreme small amounts of form I have been observed to spontaneously transform into form II in a time interval of about six years at room temperature and it can be concluded that although form I is very persistent under ambient conditions, it does slowly convert into form II. Moreover, the system does not obey the density rule., Peer Reviewed, Postprint (author's final draft)

Plastic crystals are currently attracting interest because their solid-state caloric functionality could be used to tackle climate change in two critical areas: (i) more environmentally friendly cooling and heating driven by pressure and (ii) passive waste heat management. Here, we suggest that plastic crystals could also be used for active pressure-assisted (i.e., barocaloric) waste heat management. In contrast to the barocaloric cooling/heating cycle, for active barocaloric waste heat management, the hysteresis may not be a constraint and transition temperatures above ambient are usually desired. In contrast to passive waste heat management, the application of pressure can be an advantage to actively control the absorption and delivery of heat by the plastic crystal. Here, we have investigated the pressure-induced caloric response at the first-order phase transitions occurring above room temperature of three plastic crystals derived from adamantane: 1-adamantanol, 2-adamantanol, and 2-methyl-2-adamantanol. Colossal barocaloric effects have been found for two of them under small pressure changes of 50 MPa. This behavior occurs thanks to a colossal transition entropy change and a large transition sensitivity to pressure, which can simultaneously take place due to enormous transition volume changes. The balance between configurational and volumic entropy changes at the transition has also been discussed. For 2-adamantanol, in addition to the transition to the plastic phase, the less energetic triclinic-to-monoclinic transition at lower temperatures has also been analyzed. The transition temperatures above ambient make these compounds suitable for waste heat management and, thanks to a small hysteresis, also for industrial cooling and heat pumping., Peer Reviewed, Postprint (published version)

The polymorphic behavior at normal pressure as a function of temperature of 2-adamantanol (C10H16O) and 2-methyl-2-adamantanol (C11H18O) has been investigated by single-crystal and powder X-ray diffraction as well as differential scanning calorimetry. Our findings demonstrate that the previously reported specific heat anomaly at around 238 K for C10H16O consists of a single-crystal to single-crystal IV–III high-order phase transition without change of space group (P[1 with combining macron], Z = 6, Z' = 3). The combined use of single-crystal and powder X-ray diffraction demonstrates that phase IV would be fully ordered only at 0 K. As the temperature increases, the hydrogen atoms linked to the oxygen atoms are found to be disordered between two sites, reaching an occupancy factor of 50% each at the IV–III transition temperature. An order parameter related to the continuous change of the ß lattice parameter can account for this IV–III high-order phase transition. Furthermore, a mechanism is proposed for the first-order transition from phase III to phase II (monoclinic, C2/m, Z = 12, Z' = 1.5), in which O atoms are disordered between 2 sites (50% occupancy factor). Single-crystal X-ray diffraction of the low-temperature phase of C11H18O, stable below 368 K, shows unambiguously a fully ordered orthorhombic structure (Pbcn, Z = 16, Z' = 2), contrary to the previously reported space group (Pcc2). Below melting temperature, both compounds display a high-temperature orientationally disordered (plastic) phase (Fm[3 with combining macron]m, Z = 4), like most of the adamantane derivatives., Peer Reviewed, Postprint (author's final draft)

Aquest article presenta el desenvolupament i primers resultats d'ús d'un conjunt de cursos virtuals que pretenen proporcionar uns coneixements inicials bàsics de Matemàtiques, Física i !ímica als estudiants que accedeixen a estudis de grau a l'Escola d'Enginyeria de Barcelona Est (EEBE). Els cursos han estat desenvolupats sobre la plataforma Atenea (Moodle). El seu nucli el constitueixen un conjunt de materials per a autoaprenentatge que inclouen documents escrits, vídeos i tests d'autoavaluació. Els documents escrits i els vídeos corresponen tant a explicacions de teoria com a la resolució detallada d'exercicis. En el marc d'una prova pilot, els cursos, de seguiment voluntari durant el període transcorregut entre la matricula (mitjans de juliol) i l'inici de les classes (mitjans de setembre), van ser publicitats a tots els estudiants de nou accés del curs 2021-2022. Encara que la participació va ser més limitada del que s'esperava (únicament el 22% dels estudiants de nou accés es van inscriure), cal destacar que els estudiants que sí que van seguir els cursos van expressar majoritàriament una bona valoració dels mateixos (al respondre un qüestionari de satisfacció). Del desenvolupament dels cursos i de la realització de la prova pilot s'han obtingut unes quantes conclusions que també queden reflectides al final de l'article.

The phase behaviour of drug molecules is important for the control over the desired polymorph in drug formulations, whether it is to ensure better stability or better solubility. In the case of pyrazinamide, a drug against tuberculosis, stability studies have been complicated due to the very slow transition kinetics observed in DSC measurements. Using vapour pressure measurements, in which the reluctance of phase transformation is in fact an advantage, all solid–solid phase transformation temperatures have been determined. This method has been key to map the phase behaviour of pyrazinamide. The use of high-pressure measurements with synchrotron X-ray diffraction has allowed the construction of the pressure–temperature phase diagram of the four solid phases of pyrazinamide and the liquid phase. The a form was found to be the stable form at room temperature. One striking feature of pyrazinamide is that one polymorph, the d form, has a very large thermal expansion and extreme compressibility not found in the other three forms. This gives rise to curved solid–solid transition equilibria in the pressure–temperature phase diagram, which is not commonly observed in the pressure range of 0 to 1 GPa. Using the phase diagram, polymorph ß could be obtained in its stable temperature domain., Peer Reviewed, Postprint (published version)

The structure of the metastable form II of 2-bromobenzophenone, obtained by crystallization from the melt, has been determined by powder X-ray diffraction. Form II has been solved in the centrosymmetric monoclinic space group P21/c with a = 8.4896(19) Å, b = 6.5438(8) Å, c = 20.253(1) Å; ß = 104.452(6)°, and Z = 4 (Z' = 1) at 200 K. Both form I and form II contain a multitude of aromatic interactions, and the strength and direction of these interactions could only be interpreted with the support of the thermal-expansion tensors. Both forms exhibit, unexpectedly, uniaxial negative thermal expansion, while hydrogen bonding does not play a significant role in either of these two structures. It appears to be the first time in the literature that uniaxial negative thermal expansion may be caused by aromatic interactions. Thermodynamic properties at normal and high pressure have been determined for the stable and metastable phases, and a pressure–temperature phase diagram has been constructed. While the metastable form behaves monotropically with respect to the stable form under ambient conditions, the phase relationship becomes enantiotropic at high pressure, providing a clear example of phase behavior in which the densest form is not the most stable form under ambient conditions., Peer Reviewed, Postprint (author's final draft)

Barocaloric effects in a layered hybrid organic–inorganic compound, (C10H21NH3)2MnCl4, that are reversible and colossal under pressure changes below 0.1 GPa are reported. This barocaloric performance originates in a phase transition characterized by different features: A strong disordering of the organic chains, a very large volume change, a very large sensitivity of the transition temperature to pressure and a small hysteresis. The obtained values are unprecedented among solid-state cooling materials at such low pressure changes and demonstrate that colossal effects can be obtained in compounds other than plastic crystals. The temperature-pressure phase diagram displays a triple point indicating enantiotropy at high pressure., Peer Reviewed, Postprint (published version)

The crystal structures of dimorphic benzylthiouracil, a drug against hyperthyroidism, have been redetermined and the atom coordinates of the two independent molecules of form I have been obtained for the first time. The dimorphism convincingly demonstrates the conformational versatility of the benzylthiouracil molecule. It has been established through calorimetric studies that the low-temperature form II transforms endothermically (¿II¿IH = 5.6(1.5) J g-1) into form I at 405.4(1.0) K. The high-temperature form I melts at 496.8(1.0) K (¿I¿LH = 152.6(4.0) J g-1). Crystallographic and thermal expansion studies show that form II is denser than form I, leading to the conclusion that the slope of the II-I equilibrium curve in the pressure-temperature phase diagram is positive. It follows that this dimorphism corresponds to a case of overall enantiotropic behaviour, which implies that both solid phases possess their own stable phase region irrespective of the pressure. Moreover, form II is clearly the stable polymorph under ambient conditions., Peer Reviewed, Postprint (author's final draft)

A giant barocaloric effect (BCE) in a molecular material Fe3(bntrz)6(tcnset)6 (FBT) is reported, where bntrz = 4-(benzyl)-1,2,4-triazole and tcnset = 1,1,3,3-tetracyano-2-thioethylepropenide. The crystal structure of FBT contains a trinuclear transition metal complex that undergoes an abrupt spin-state switching between the state in which all three FeII centers are in the high-spin (S = 2) electronic configuration and the state in which all of them are in the low-spin (S = 0) configuration. Despite the strongly cooperative nature of the spin transition, it proceeds with a negligible hysteresis and a large volumetric change, suggesting that FBT should be a good candidate for producing a large BCE. Powder X-ray diffraction and calorimetry reveal that the material is highly susceptible to applied pressure, as the transition temperature spans the range from 318 at ambient pressure to 383 K at 2.6 kbar. Despite the large shift in the spin-transition temperature, its nonhysteretic character is maintained under applied pressure. Such behavior leads to a remarkably large and reversible BCE, characterized by an isothermal entropy change of 120 J kg-1 K-1 and an adiabatic temperature change of 35 K, which are among the highest reversible values reported for any caloric material thus far., Postprint (published version)

Morniflumate diniflumate, a molecular compound involving niflumic acid and its ß-morpholino ethyl ester (morniflumate) in the mole ratio 2:1, is found to crystallize in a triclinic P - 1 space group with a unit-cell volume of 2203.4(5) Å3. It is a cocrystal between a morniflumate+ niflumate- salt and a neutral niflumic acid molecule. The co-crystalline salt forms endothermically with a positive excess volume and it melts incongruently at 382.3(8) K. Differential scanning calorimetry executed at heating rates above 20 K·min-1, leads to congruent melting at 387.8(9)K with an enthalpy change of ¿fusH = 80(2) J g-1. The rare occurrence that incongruent and congruent melting can be observed for the same cocrystal may be due to the conformational versatility of the niflumic acid molecule and its slow conversion between the different conformations due to weak intramolecular hydrogen bonding., Peer Reviewed, Postprint (author's final draft)

The crystal structure of the low-temperature form II of butamben has been solved in a P21/c space group very similar to that of form I. Form II possesses virtually the same packing as that of the high-temperature form I, and the dimorphism is mainly represented by a small discontinuous change in the size of the unit cell and by a difference in the enthalpy. Because of the small enthalpy difference between the two polymorphs of 375 J·mol–1, it will be difficult to predict the change in the stability hierarchy by computer-aided methods. The pressure–temperature phase diagram, constructed using volume and enthalpy differences between the two phases at ordinary pressure, corresponds to a case of overall enantiotropy, as the I–II and I–L equilibrium lines diverge with increasing pressure. This conclusion is confirmed by the experimental pressure–temperature phase diagram obtained with differential thermal analysis measurements under pressure, Peer Reviewed, Postprint (author's final draft)

Chemical derivatization and amorphization are two possible strategies to improve the solubility and bioavailability of drugs, which is a key issue for the pharmaceutical industry. In this contribution, we explore whether both strategies can be combined by studying how small differences in the molecular structure of three related pharmaceutical compounds affect their crystalline structure and melting point (Tm), the relaxation dynamics in the amorphous phase, and the glass transition temperature (Tg), as well as the tendency toward recrystallization. Three benzodiazepine derivatives of almost same molecular mass and structure (Diazepam, Nordazepam and Tetrazepam) were chosen as model compounds. Nordazepam is the only one that displays N–H···O hydrogen bonds both in crystalline and amorphous phases, which leads to a significantly higher Tm (by 70–80 K) and Tg (by 30–40 K) compared to those of Tetrazepam and Diazepam (which display similar values of characteristic temperatures). The relaxation dynamics in the amorphous phase, as determined experimentally using broadband dielectric spectroscopy, is dominated by a structural relaxation and a Johari–Goldstein secondary relaxation, both of which scale with the reduced temperature T/Tg. The kinetic fragility index is very low and virtually the same (mp ˜ 32) in all three compounds. Two more secondary relaxations are observed in the glass state: the slower of the two has virtually the same relaxation time and activation energy in all three compounds, and is assigned to the inter-enantiomer conversion dynamics of the flexible diazepine heterocycle between isoenergetic P and M conformations. We tentatively assign the fastest secondary relaxation, present only in Diazepam and Tetrazepam, to the rigid rotation of the fused diazepine–benzene double ring relative to the six-membered carbon ring. Such motion appears to be largely hindered in glassy Nordazepam, possibly due to the presence of the hydrogen bonds. Supercooled liquid T, Peer Reviewed, Postprint (author's final draft)

The volume change on melting is a rarely studied quantity and it is not well understood even if it must reflect the changes in interaction between the solid and the liquid state. It is part of the solid-state information for materials and pharmaceuticals and it is important for the reliability of polymorph stability study results. Using the crystal structure of monoclinic tetrazepam at 150 K and at room temperature, in addition to powder X-ray diffraction as a function of the temperature, the specific volume of tetrazepam has been determined over a large temperature domain. In combination with a pressure-temperature curve for the melting of tetrazepam, its volume change on melting could be determined. With this information and previous data from the literature, the assumption that the volume of the solid increases on average with 11% on melting has been investigated. It can be concluded that this value is not constant; however so far, no simple relationship has been found to relate the solid state to its volume change on melting and using 11% remains best practice. A comparison of the tetrazepam crystal structure with diazepam and nordiazepam has been provided too., Peer Reviewed, Postprint (author's final draft)

Plastic crystals undergo phase transitions with unusually large volume and entropy changes related to strong molecular orientational disordering. These features have led to a resurgent interest in these materials because recently they have shown great potential in solid-state cooling applications driven by pressure. Here we demonstrate that two plastic crystals derived from adamantane -1-Br-adamantane and 1-Cl-adamantane- undergo colossal reversible barocaloric effects under moderate pressure changes in a wide temperature span near room temperature thanks to a relatively small hysteresis and very high sensitivity of the transition temperature to pressure. In particular, 1-Cl-adamantane displays an optimal operational temperature range covering from ~40 K below and up to room temperature, and under a pressure change of 1 kbar this compound outperforms any other barocaloric material known so far. Our work gives strong support to plastic crystals as best candidates for barocaloric cooling. We also provide insight into the physical origin of the entropy changes through the analysis of the disorder on the involved phases., Peer Reviewed, Postprint (author's final draft)

Solid-state cooling methods based on field-driven first-order phase transitions are often limited by significant hysteresis and small temperature span, which increase the input work required to drive the cooling cycle reversibly and reduce the temperature range of operation. Here we show that giant reversible caloric effects can be driven using low hydrostatic pressures in the molecular crystal of fullerene C60 across its order–disorder first-order phase transition due to a small transition hysteresis and a high sensitivity of the transition to pressure. In particular, we obtain isothermal entropy changes ¿S = 25 J K-1 kg-1 under reversible application and removal of a pressure as low as p = 0.05 GPa. We also demonstrate that these features allow us to obtain these giant effects in a wide temperature span around room temperature which, furthermore, is desirable for single-component regenerative coolers. For a pressure change of p = 0.41 GPa, we obtain giant reversible values of ¿S = 31 J K-1 kg-1 and ¿T = 11 K, in a temperature interval larger than 50 K. This very good barocaloric performance postulates C60 as one of the best candidates known so far to be considered by engineers for the development of barocaloric devices. The physics underlying these caloric effects is also analyzed., Peer Reviewed, Postprint (author's final draft)

Aquest treball té com a objectiu l’estudi del polimorfisme, l’habilitat d’un sòlid d’existir en més d’una estructura cristal·lina, per dos materials orgànics que constitueixen ingredients actius farmacèutics amb propietats analgèsiques locals. Aquests materials moleculars són el butamben i l’isobutamben. L’estudi estableix els dominis d’estabilitat de les diferents fases sòlides polimòrfiques en el pla pressió-temperatura mitjançant l’estudi experimental i la seva compatibilitat amb el càlcul topològic. La determinació dels dominis d’estabilitat i, en conseqüència, de les transicions de fase entre els diferents polimorfs, així com els processos de fusió, tots en funció de la pressió, s’han dut a terme mitjançant tècniques calorimètriques a pressió normal i a alta pressió. Aquest conjunt de dades experimentals permet establir el diagrama pressió-temperatura i per tant el domini d’estabilitat de cadascuna de les fases. A través de la difracció de raig X s’han determinat els volums dels diferents polimorfs en funció de la temperatura a pressió normal i les variacions de volum en les diferents transicions sòlid-sòlid entre polimorfs. Amb relació al butamben, les relacions d’estabilitat no varien respecte a la pressió, les dues formes cristal·lines tenen un domini d’estabilitat concret i es pot passar d’una a l’altra de forma completament reversible; és a dir, és un cas d’enantiotropia entre les dues formes. D’altra banda, en el cas de l’isobutamben les relacions d’estabilitat varien en funció de la pressió, a baixes pressions presenta el mateix comportament que el butamben, enantiotriopia, i, en canvi, a altes pressions només hi ha una forma estable en tot el rang de pressions i no és possible passar d’una a l’altra de forma reversible, és a dir, una de les formes es comporta monotròpicament respecte a l’altra., Este trabajo tiene como objetivo el estudio del polimorfismo, la habilidad de un sólido de existir en más de una estructura cristalina, por dos materiales orgánicos que constituyen ingredientes activos farmacéuticos con propiedades analgésicas locales. Estos materiales moleculares son el butamben y el isobutamben. El estudio establece los dominios de estabilidad de las diferentes fases sólidas polimórficas en el plano presión-temperatura mediante el estudio experimental y su compatibilidad con el cálculo topológico. La determinación de los dominios de estabilidad y, en consecuencia, de las transiciones de fase entre los diferentes polimorfos, así como los procesos de fusión, todos en función de la presión, se han llevado a cabo mediante técnicas calorimétricas a presión normal y a alta presión. Este conjunto de datos experimentales permite establecer el diagrama presión-temperatura y por tanto el dominio de estabilidad de cada una de las fases. A través de la difracción de rayo X se han determinado los volúmenes de los diferentes polimorfos en función de la temperatura a presión normal y las variaciones de volumen en las diferentes transiciones sólido-sólido entre polimorfos. Con relación al butamben, las relaciones de estabilidad no varían respeto a la presión, las dos formas cristalinas tienen un dominio de estabilidad concreto y se puede pasar de una a la otra de forma completamente reversible; es decir, es un caso de enantiotroía entre las dos formas. Por otro lado, en el caso del isobutamben las relaciones de estabilidad varían en función de la presión, a bajas presiones presenta el mismo comportamiento que el butamben, mientras que, a altas presiones, sólo hay una forma estable en todo el rango de presiones y no es posible pasar de una a la otra de forma reversible, es decir, una de las formas se comporta monotrópicamente respecto la otra., This work aims to study polymorphism, the ability of a solid to exist in more than one crystalline structure, by two organic materials that constitute active pharmaceutical ingredients with local analgesic properties. These molecular materials are butamben and isobutamben. The study establishes the stability domains of the different polymorphic solid phases in the pressure-temperature plane by means of the experimental study and their compatibility with the topological calculation. The determination of the stability domains and, consequently, of the phase transitions between the different polymorphs, as well as the melting processes, all of them as a function of pressure, have been carried out by means of calorimetric techniques at normal pressure and at high pressure. This set of experimental data allows establishing the pressure-temperature diagram and therefore the stability domain of each of the phases. Through X-ray diffraction, the volumes of the different polymorphs have been determined as a function of the temperature at normal pressure and the volume variations in the different solid-solid transitions between polymorphs. In relation to butamben, the stability relations do not vary with respect to pressure, the two crystalline forms have a specific stability domain and one can pass from one to the other in a completely reversible way, i.e., the relationship between both forms is enantiotropic. On the other hand, as for the isobutamben, the stability relations vary according to the pressure, while at low pressures it shows the same behaviour as the butamben (enantiotropy), at high pressures, there is only one stable form in the whole range of pressures and it is not possible to pass from one to the other in a reversible way, i.e., there is a monotropic relationship between both forms.

The extremely large latent heat exchanged in phase transitions involving strong molecular orientational disordering has recently led to the proposal of plastic crystals as a feasible solution for solid-state barocaloric eco-friendly cooling technologies. Here we determine the reversible barocaloric response of four plastic crystals derived from neopentane [C(CH3)4]: (NH2)C(CH2OH)3 (TRIS for short), (NH2)(CH3) C(CH2OH)2 (AMP), (CH3)C(CH2OH)3 (PG) and (CH3)3C(CH2OH) (NPA). All of them display colossal entropy changes at their ordered-plastic phase transition, which is a primal requirement for competitive barocaloric materials. However, we show that it is also important to verify that the large barocaloric effects can be achieved using pressures that, while being moderate, are large enough to overcome the pressure-dependent hysteresis. From this quantity and using the quasi-direct method, we determine the minimum pressure needed to achieve reversible barocaloric effects, prev, for each compound. Specifically, we find a small and moderate prev for PG and NPA, respectively, which therefore display colossal reversible barocaloric effects comparable to harmful fluids used in current refrigerators and thus confirm the potential of plastic crystals as excellent alternatives. Instead, in TRIS and AMP, the obtained prev is excessive to yield reversible barocaloric effects useful for cyclic applications., Peer Reviewed, Postprint (author's final draft)

Pyrazinamide is an active pharmaceutical compound for the treatment of tuberculosis. It possesses at least four crystalline polymorphs. Polymorphism may cause solubility problems as the case of ritonavir has clearly demonstrated; however, polymorphs also provide opportunities to improve pharmaceutical formulations, in particular if the stable form is not very soluble. The four polymorphs of pyrazinamide constitute a rich system to investigate the usefulness of metastable forms and their stabilization. However, despite the existence of a number of papers on the polymorphism of pyrazinamide, well-defined equilibrium conditions between the polymorphs appear to be lacking. The main objectives of this paper are to establish the temperature and pressure equilibrium conditions between the so-called a and ¿ polymorphs of pyrazinamide, its liquid phase, and vapor phase and to determine the phase-change inequalities, such as enthalpies, entropies, and volume differences. The equilibrium temperature between a and ¿ was experimentally found at 392(1) K. Moreover, vapor pressures and solubilities of both phases have been determined, clearly indicating that form a is the more stable form at room temperature. High-pressure thermal analysis and the topological pressure–temperature phase diagram demonstrate that the ¿ form is stabilized by pressure and becomes stable at room temperature under a pressure of 260 MPa., Peer Reviewed, Postprint (author's final draft)

The polymorphism of 1,3-dimethyladamantane (13DMA), 1,3-adamantanediol (13DOHA) and 1,3-dibromoadamantane (13DBrA) has been studied by X-ray powder diffraction, density measurements and differential scanning calorimetry at normal and high-pressure. 13DMA exhibits a low-temperature ordered monoclinic phase (space group P21/c, Z = 4, Z' = 1) which transforms at 222.6 ± 0.5 K into a high-temperature hexagonal plastic phase (P63/mmc, Z = 26), stable up to the melting point at 246.8 ± 0.5 K at normal pressure. 13DOHA exhibits a low-temperature hexagonal phase (P63/mcm, Z = 6, Z' = 0.25) which transforms into a face-centered cubic plastic phase (Fm[3 with combining macron]m). 13DBrA exhibits a unique ordered orthorhombic phase (Pnma, Z = 4, Z' = 0.5) which remains till the melting point at 382.1 ± 0.5 K. The stability temperature domain of the plastic phases increases with pressure for both 13DMA and 13DOHA. The ability to form the plastic phase for these compounds as well as a series of adamantanes derivatives is analysed through the globularity and asphericity parameters derived from the Hirshfeld surface analysis., Peer Reviewed, Postprint (author's final draft)

A facile, environment-friendly, versatile and reproducible approach to the successful oxidation of fullerenes (oxC60) and the formation of highly hydrophilic fullerene derivatives is introduced. This synthesis relies on the widely known Staudenmaier’s method for the oxidation of graphite, to produce both epoxy and hydroxy groups on the surface of fullerenes (C60) and thereby improve the solubility of the fullerene in polar solvents (e.g. water). The presence of epoxy groups allows for further functionalization via nucleophilic substitution reactions to generate new fullerene derivatives, which can potentially lead to a wealth of applications in the areas of medicine, biology, and composite materials. In order to justify the potential of oxidized C60 derivatives for bio-applications, we investigated their cytotoxicity in vitro as well as their utilization as support in biocatalysis applications, taking the immobilization of laccase for the decolorization of synthetic industrial dyes as a trial case., Peer Reviewed, Postprint (published version)

To decide whether an active pharmaceutical ingredient can be used in its amorphous form in drug formulations, often the glass transition is studied in relation to the melting point of the pharmaceutical. If the glass transition temperature is high enough and found relatively close to the melting point, the pharmaceutical is considered to be a good glass former. However, it is obviously important that the observed melting point and glass transition involve exactly the same system, otherwise the two temperatures cannot be compared. Although this may seem trivial, in the case of hydrates, where water may leave the system on heating, the composition of the system may not be evident. Atorvastatin calcium is a case in point, where confusing terminology, absence of a proper anhydrate form, and loss of water on heating lead to several doubtful conclusions in the literature. However, considering that no anhydrate crystal has ever been observed and that the glass transition of the anhydrous system is found at 144 °C, it can be concluded that if the system is kept isolated from water, the chances that atorvastatin calcium crystallises at room temperature is negligible. The paper discusses the various thermal effects of atorvastatin calcium on heating and proposes a tentative binary phase diagram with water., Peer Reviewed, Postprint (author's final draft)

We have studied the barocaloric properties associated with the martensitic transition of a shape memory Heulser alloy Ni50Mn31.5Ti18.5 which is composed of all-d-metal elements. The composition of the sample has been tailored to avoid long range ferromagnetic order in both ausenite and martensite. The lack of ferromagnetism results in a weak magnetic contribution to the total entropy change thereby leading to a large transition entropy change. The combination of such a large entropy change and a relatively large volume change at the martensitic transition gives rise to giant barocaloric properties in this alloy. When compared to other shape memory Heusler alloys, our material exhibits values for adiabatic temperature and isothermal entropy changes significantly larger than values reported so far for this class of materials. Furthermore, our Ni50Mn31.5Ti18.5 also compares favourably to the best state-of-the-art magnetic barocaloric materials., Peer Reviewed, Postprint (author's final draft)

MnNiSi-based alloys and isostructural systems have traditionally demonstrated impressive magnetocaloric properties near room temperature associated with a highly tunable first-order magnetostructural transition that involves large latent heat. However, these materials are limited by a small field-sensitivity of the transition, preventing significant reversible effects usable for cooling applications. Instead, the concomitant large transition volume changes prompt a high pressure-sensitivity, and therefore, promise substantial barocaloric performances, but they have been sparsely studied in these materials. Here, we study the barocaloric response in a series of composition-related (MnNiSi)1-x(FeCoGe)x (x = 0.39, 0.40, 0.41) alloys that span continuously over a wide temperature range around ambient. We report on giant reversible effects of ~40 J K-1 kg-1 and up to ~4 K upon application of ~2 kbar and find a degradation of the first-order transition properties with pressure that limits the barocaloric effects at high pressures. Our results confirm the potential of this type of alloys for barocaloric applications, where multicaloric and composite possibilities, along with the high density and relatively high thermal conductivity, constructively add to the magnitude of the caloric effects., Peer Reviewed, Postprint (published version)

The formation of co-crystals is often unexpected; however, the Buckminster fullerene, for which many solvates are known,is an excellent system to study this tendency. In the present paper, C60 and CBrCl2H co-crystals have been studied. Hexagonal P6/mmmC60·2CBrCl2H co-crystals transform at 373 K to monoclinic C2/c C60·CBrCl2H co-crystals. While orientational disorder typical for C60 is found in the hexagonal co-crystals (as found in many C60 halomethane solvates), in the monoclinic co-crystals, C60 appears to be orientationally ordered. As for the solvent CBrCl2H, two types of occupational disorder involving the distribution of the halogen atoms can be observed, comparable to the behaviour in the two polymorphs of pure CBrCl2H. Within the monoclinic solvate, two sites are equally occupied by Br and Cl atoms (1/2:1/2), while one site is fully occupied by a Cl atom which leads to an average Cs symmetry for the solvent molecule. Whereas within the hexagonal co-crystals, each halogen position is occupied by 1/3:2/3 of Br or Cl atoms, respectively, leading to an average C3v molecular symmetry. The anisotropy of the intermolecular interactions coincides with the symmetry of the solvate structures and can be generalized for the C60·halomethane co-crystals., Peer Reviewed, Postprint (author's final draft)

We employ calorimetry, Rietveld refinement of X-ray powder diffraction, broadband dielectric spectroscopy and molecular dynamics simulations, to investigate the phase behavior, crystal structure, dc conductivity and dielectric response of the condensed phases of ethanolamine (EAM), an ethane derivative with two distinct hydrogen-bonding groups. EAM is found to exhibit, besides its stable crystal phase, a metastable crystalline phase obtained from the supercooled liquid phase. The metastable phase can only be maintained at low temperature; upon heating an irreversible exothermic transformation to the stable crystal structure takes place at 210 K, with a low transition enthalpy of ca. 2.4 J/g. The observed polymorphism is accompanied by differences in the molecular conformation and degree of structural order. Each EAM molecule participates in six H-bonds in both crystalline phases. While the stable phase is fully ordered, the metastable phase appears to be characterized by a statistical disorder in the position of the hydrogen atoms and thus of the intramolecular conformation and intermolecular hydrogen bonding. Our molecular dynamics simulations suggest that such disorder is dynamic in character, and allow analyzing the dynamic H-bonding motif of the metastable phase in terms of composition, length and energy of the H-bonds, and molecular conformations involved. Charge conduction is mainly ionic in both crystalline phases and exhibits the typical temperature dependence of disordered solid electrolytes, rather than crystalline ones. Dielectric characterization indicates that, upon crystallization of liquid EAM, a small fraction of the sample (approximately 5%) remains amorphous, a situation similar to that reported for other H-bonded systems such as glycerol and nbutanol., Postprint (author's final draft)

Hydrostatic pressure represents an inexpensive and practical method of driving caloric effects in brittle magnetocaloric materials, which display first-order magnetostructural phase transitions whose large latent heats are traditionally accessed using applied magnetic fields. Here, moderate changes of hydrostatic pressure are used to drive giant and reversible inverse barocaloric effects near room temperature in the notoriously brittle magnetocaloric material MnCoGeB0.03. The barocaloric effects compare favorably with those observed in barocaloric materials that are magnetic. The inevitable fragmentation provides a large surface for heat exchange with pressure-transmitting media, permitting good access to barocaloric effects in cooling devices., Peer Reviewed, Postprint (author's final draft)

En este proyecto, se ha hecho un estudio del polimorfismo que presentan dos derivados de la benzofenona. El polimorfismo es la capacidad de una sustancia para cristalizar en más de una forma sólida. Para establecer los dominios de estabilidad de las diferentes formas, se ha determinado el diagrama de equilibrio presión-temperatura de ambos compuestos. Para la realización del estudio, se ha recurrido a la utilización de diferentes técnicas de análisis. Se ha utilizado la técnica de calorimetría diferencial de barrido, a fin de caracterizar térmicamente las transiciones entre fases que presentan cada uno de los compuestos; es decir, determinar la temperatura y la variación de entalpía asociadas a cada una de las transiciones. También se ha utilizado un sistema de análisis térmico diferencial en función de la presión, para obtener el diagrama presión-temperatura. Además, se ha empleado la difracción de rayos X, para caracterizar cristalográficamente las muestras y establecer la evolución del volumen específico con la temperatura. Durante el estudio, se han utilizado técnicas de purificación, como la cristalización por evaporación, y en algunos casos se ha tratado la muestra con N2. Los compuestos estudiados son dos, el 4-bromobenzofenona y el 2-bromobenzofenona. Ambos compuestos presentan dimorfismo a presión atmosférica. El compuesto 4-bromobenzofenona ha sido proporcionado por los laboratorios Aldrich con una pureza del 98%, mientras que el 2- bromobenzofenona ha sido proporcionado por el “B. Verkin Institute for Low Temperature Physics and Engineering” de Ucrania. Únicamente ha sido posible caracterizar completamente el 2-bromobenzofenona. Para el caso del 4- bromobenzofenona no se ha podido obtener el polimorfo metaestable y con ello ha sido imposible caracterizar por completo el compuesto.

We probe the dielectric response of the supercooled liquid phase of Morniflumate, a drug with anti-inflammatory and antipyretic properties, studying in particular the pressure and temperature dependence of the relaxation dynamics, glass transition temperature Tg, and recrystallization kinetics. Tg increases by roughly 20 K every 100 MPa at low applied pressure, where the ratio Tg/Tm has a constant value of ~0.8 (Tm = melting point). Liquid Morniflumate displays two dielectric relaxations: the structural a relaxation associated with the collective reorientational motions, which become arrested at Tg, and a secondary relaxation likely corresponding to an intramolecular dynamics. The relaxation times of both processes scale approximately with the inverse reduced temperature Tg/T. Near room temperature and under an applied pressure of 50 MPa, supercooled Morniflumate recrystallizes in a characteristic time of few hours, with an Avrami exponent of 1.15. Under these conditions, the recrystallization rate is a nonmonotonic function of temperature, displaying a maximum at around 298 K, which can be taken to be the optimum crystal growth temperature Tnose. The ß relaxation becomes kinetically frozen at ambient temperature under an applied hydrostatic pressure higher than 320 MPa, suggesting that the Morniflumate glass should be kinetically stable under these conditions., Peer Reviewed, Postprint (author's final draft)

There is currently great interest in replacing the harmful volatile hydrofluorocarbon fluids used in refrigeration and air-conditioning with solid materials that display magnetocaloric, electrocaloric or mechanocaloric effects. However, the field-driven thermal changes in all of these caloric materials fall short with respect to their fluid counterparts. Here we show that plastic crystals of neopentylglycol (CH3)2C(CH2OH)2 display extremely large pressuredriven thermal changes near room temperature due to molecular reconfiguration, that these changes outperform those observed in any type of caloric material, and that these changes are comparable with those exploited commercially in hydrofluorocarbons. Our discovery of colossal barocaloric effects in a plastic crystal should bring barocaloric materials to the forefront of research and development in order to achieve safe environmentally friendly cooling without compromising performance., Peer Reviewed, Postprint (published version)

We employ differential scanning calorimetry, IR spectroscopy, X-ray powder diffraction and dielectric spectroscopy to characterize binary mixtures of m-fluoroaniline (mFA), a rigid-molecule glass former, with two non-self-associating molecules containing benzene rings, namely m-xylene (mX) and a distyrene derivative (DS). The addition of mX suppresses the formation of H-bonded mFA clusters. While both mX and DS dilute the H-bond density of mFA, they have opposite effects on the glass transition temperature (Tg) and structural relaxation time of mFA, with mX acting as a plasticiser and DS as an antiplasticiser. While the mFA-DS mixtures can be studied in the supercooled liquid regime at DS molar mass fraction as high as 0.9 without undergoing phase separation, the mFA-mX mixtures remain homogeneous at low temperatures only up to a mX molar fraction of 0.5. All homogeneous mixtures display a structural relaxation which shifts according to the Tg of the mixture, and a secondary relaxation which remains virtually invariant with respect to that of pure mFA. For mX molar fraction higher than 0.5, the mixtures phase-separate into almost pure crystalline mX domains and a mFA-rich amorphous phase. Upon partial crystallization the structural relaxation time and Tg of the remaining amorphous fraction shift to larger values, consistent with the increased effective mFA concentration. At the same time, the secondary relaxation time undergoes a dramatic shift of more than two decades. These findings allow identifying the secondary relaxation in the rigid-molecule mFA glass former as a local reorientational motion of a m-fluoroaniline moiety around one of its H-bonds, a rotation that is strongly affected if the mobility of the H-bond sharing species is quenched by crystallization., Peer Reviewed, Postprint (author's final draft)

The dynamics of a simple and rigid molecule (2-chlorothiophene) has been studied by means of broadband dielectric spectroscopy (BDS) within the low-temperature stable crystalline phase, whose structure has been determined by means of powder X-ray diffraction (PXRD) measurements. The triclinic P1 structure consists of two molecules per asymmetric unit (Z' = 2) with site occupancies of 80:20 and 60:40 for each molecule of the asymmetric unit. Such a statistical intrinsic disorder is associated with two dynamical relaxation processes corresponding respectively to out-of-plane relaxations around the C–Cl 2-fold molecular axis and in-plane reorientational motions as proposed previously (Fujiromi and Oguni, J. Phys. Chem. Solids 1993, 54, 437-612). The PXRD and BDS measurements allow rationalizing published nuclear quadrupole resonance data. We show that only the concurrent use of different experimental techniques provides the answer to a complicated case of orientational molecular dynamics in the solid state., Peer Reviewed, Postprint (author's final draft)

Information about the solid-state properties of etifoxine has been lacking, even if the active pharmaceutical ingredient has been used for its anxiolytic properties for decennia. The crystal structure of the racemic compound possesses a monoclinic space group P21/n with cell parameters a¿=¿8.489(2) Å, b¿=¿17.674(2) Å, c¿=¿20.883(3) Å, ß¿=¿98.860(10)° and a unit-cell volume of 3095.8(9) Å3 at 293¿K. The unit cell contains 8 molecules, while 2 independent molecules with different conformations are present in the asymmetric unit. The density of the crystal is 1.291¿g/cm3 and its melting point was found at 362.6¿±¿0.3¿K with a melting enthalpy of 85.6¿±¿3.0¿J¿g-1. Its thermal expansion in the liquid and the solid state and the change in volume on melting and between the vitreous state and the crystalline solid have been studied. The results confirm the tendency of small organic molecules to increase about 11% in volume on melting, while the volume difference between the glass and the crystal at the glass transition temperature is about half this value at 6%. These values can be used in the construction of phase diagrams in the case that the experimental data for a given system is incomplete., Peer Reviewed, Postprint (author's final draft)

Since the early nineties countless publications have reported promising medicinal applications for [60]fullerene (C60) related to its unparalleled affinity towards free radicals. Yet, until now no officially approved C60-based drug has reached the market, notably because of the alleged dangers of C60. Nevertheless, since the publication of the effects of C60 on the lifespan of rodents, a myriad of companies started selling C60 worldwide for human consumption without any approved clinical trial. Nowadays, several independent teams have confirmed the safety of pure C60 while demonstrating that previously observed toxicity was due to impurities present in the used samples. However, a purity criterion for C60 samples is still lacking and there are no regulatory recommendations on this subject. In order to avoid a public health issue and for regulatory considerations, a quality-testing strategy is urgently needed. Here we have evaluated several analytical tools to verify the purity of commercially available C60 samples. Our data clearly show that differential scanning calorimetry is the best candidate to establish a purity criterion based on the sc-fcc transition of a C60 sample (Tonset 258 K, Dsc-fccH 8 J g¿1)., Peer Reviewed, Postprint (published version)

Peer Reviewed, Postprint (published version)

Postprint (author's final draft)

Postprint (author's final draft)

The co-crystal of C60·2CBrClH2 possesses a monoclinic (C2/m) structure at room temperature with both molecular entities, C60 and CBrClH2, orientationally ordered. At 322 K, it transforms reversibly into a hexagonal (P6/mmm) setting, revealing a rare example of a heteromolecular stator–rotator transition in a fullerene co-crystal, which applies to both the fullerene and the coformer analogous to the paradigmatic C60–cubane co-crystal. However, in the present case, topological molecular surface matching between the two chemical species is not necessary and the order–disorder phase transition reflects simultaneous activation of the orientational disorder of both C60 and CBrClH2., Peer Reviewed, Postprint (author's final draft)

The temperature-composition phase diagram of the two-component system 1-Br-adamantane and 1-Cl-adamantane has been determined by means of thermal analysis techniques and X-ray powder diffraction from the low-temperature phase to the liquid state. The crossed isopolymorphism formalism has been applied to the two-component system to infer the normal pressure properties of the orthorhombic metastable phase of 1-Cl-adamantane at normal pressure. The experimental pressure-temperature phase diagrams for the involved compounds are related to the two-phase equilibria determined at normal pressure and inferences about the monotropic behavior of the aforementioned orthorhombic phase are discussed., Peer Reviewed, Postprint (author's final draft)

Postprint (author's final draft)

Current interest in barocaloric effects has been stimulated by the discovery that these pressure-driven thermal changes can be giant near ferroic phase transitions in materials that display magnetic or electrical order. Here we demonstrate giant inverse barocaloric effects in the solid electrolyte AgI, near its superionic phase transition at ~420 K. Over a wide range of temperatures, hydrostatic pressure changes of 2.5 kbar yield large and reversible barocaloric effects, resulting in large values of refrigerant capacity. Moreover, the peak values of isothermal entropy change (60 J K-1 kg-1 or 0.34 J K-1 cm-3) and adiabatic temperature changes (18 K), which we identify for a starting temperature of 390 K, exceed all values previously recorded for barocaloric materials. Our work should therefore inspire the study of barocaloric effects in a wide range of solid electrolytes, as well as the parallel development of cooling devices., Peer Reviewed, Postprint (published version)

Understanding the polymorphic behavior of active pharmaceutical ingredients is important for formulation purposes and regulatory reasons. Metacetamol is an isomer of paracetamol and it similarly exhibits polymorphism. In the present article, it has been found that one of the polymorphs of metacetamol is only stable under increased pressure, which has led to the conclusion that metacetamol like paracetamol is a monotropic system under ordinary (= laboratory) conditions and that it becomes enantiotropic under pressure with the I-II-L triple point coordinates for metacetamol TI-II-L = 535 ± 10 K and PI-II-L = 692 ± 70 MPa. However, whereas for paracetamol the enantiotropy under pressure can be foreseen, because the metastable polymorph is denser, in the case of metacetamol this is not possible, as the metastable polymorph is less dense than the stable one. The existence of the stability domain for the less dense polymorph of metacetamol can only be demonstrated by the construction of the topological phase diagram as presented in this article. It is a delicate interplay between the specific volume differences and the enthalpy differences causing the stability domain of the less dense polymorph to be sandwiched between the denser polymorph and the liquid. Metacetamol shares this behavior with bicalutamide and fluoxetine nitrate., Peer Reviewed, Preprint