Dynamics and local ordering of pentachloronitrobenzene: a molecular-dynamics investigation.

Plastic phases are constituted by molecules whose centers of mass form a long range ordered crystalline lattice, but rotate in a more or less constrained way. Pentachloronitrobenzene (PCNB) is a quasi-planar hexa-substituted benzene formed by a benzene ring decorated with a -NO2 group and five chlorine atoms that displays below the melting point a layered structure of rhombohedral (R3̄) planes in which the molecules can rotate around a six-fold-like axis. Dielectric spectroscopy [Romanini et al., The Journal of Physical Chemistry C, 2016, 120, 10614] of this highly anisotropic phase revealed a complex relaxation dynamics with two coupled primary α processes, initially ascribed to the in-plane and out-of-plane components of the molecular dipole. In this work, we perform a series of molecular dynamics simulations together with single crystal X-ray synchrotron diffraction experiments to investigate the puzzling dynamics of PCNB. We conclude that the molecule undergoes very fast movements due to the high flexibility of the -NO2 group, and two slower movements in which only the in-plane rotation of the whole ring is involved. These two movements are related to fast attempts to perform a 60° in-plane rotation, and a diffusive motion that involves the rotation of the molecule completely decorrelating the dipole orientation. We have also investigated whether a homogeneous or a heterogeneous scenario is better suited to describe the restricted orientational disorder of this anisotropic phase both from a structural and dynamical point of view.

Dielectric Spectroscopy Studies of Conformational Relaxation Dynamics in Molecular Glass-Forming Liquids.

We review experimental results obtained with broadband dielectric spectroscopy concerning the relaxation times and activation energies of intramolecular conformational relaxation processes in small-molecule glass-formers. Such processes are due to the interconversion between different conformers of relatively flexible molecules, and generally involve conformational changes of flexible chain or ring moieties, or else the rigid rotation of planar groups, such as conjugated phenyl rings. Comparative analysis of molecules possessing the same (type of) functional group is carried out in order to test the possibility of assigning the dynamic conformational isomerism of given families of organic compounds to the motion of specific molecular subunits. These range from terminal halomethyl and acetyl/acetoxy groups to both rigid and flexible ring structures, such as the planar halobenzene cycles or the buckled saccharide and diazepine rings. A short section on polyesters provides a generalisation of these findings to synthetic macromolecules.

Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari-Goldstein Relaxations.

Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (Tg) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher Tg, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their Tg by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the Tg of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari-Goldstein relaxation processes, one for each chemical component. Our findings have important implications for the interpretation of the Johari-Goldstein process as well as for the physical stability and mechanical properties of microfibres with small-molecule additives.

Comparative Physical Study of Three Pharmaceutically Active Benzodiazepine Derivatives: Crystalline versus Amorphous State and Crystallization Tendency.

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 Tetrazepam and Nordazepam are observed to crystallize into their stable crystalline form with an Avrami exponent close to unity indicating unidimensional growth with only sporadic nucleation, which allows a direct assessment of the crystal growth rate. Despite the very similar growth mode, the two derivatives exhibit very different kinetics for a fixed value of the reduced temperature and thus of the structural relaxation time, with Nordazepam displaying slower growth kinetics. Diazepam does not instead display any tendency toward recrystallization over short periods of time (even close to Tm). Both these observations in three very similar diazepine derivatives provide direct evidence that the kinetics of recrystallization of amorphous pharmaceuticals is not a universal function, at least in the supercooled liquid phase, of the structural or the conformational relaxation dynamics, and it is not simply correlated with related parameters such as the kinetic fragility or activation barrier of the structural relaxation. Only the crystal growth rate, and not the nucleation rate, shows a correlation with the presence or absence of hydrogen bonding.

Nose Temperature and Anticorrelation between Recrystallization Kinetics and Molecular Relaxation Dynamics in Amorphous Morniflumate at High Pressure.

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 α 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.

Tuning the Kinetic Stability of the Amorphous Phase of the Chloramphenicol Antibiotic.

We employ broadband dielectric spectroscopy to study the relaxation dynamics and crystallization kinetics of a broad-spectrum antibiotic, chloramphenicol, in its supercooled liquid form. Two dynamic processes are observed: the structural α relaxation, which becomes kinetically frozen at Tg = 302 ± 1 K, and an intramolecular secondary relaxation. Under isothermal conditions, the supercooled drug displays interconversion between different isomers, followed by recrystallization. Recrystallization follows the Avrami law with Avrami exponent n = 1.3 ± 0.1, consistent with a one-dimensional growth of crystalline platelets, as observed by electron microscopy. Exposure to humid atmosphere and subsequent heating to high temperature is found to degrade the compound. The partially degraded sample displays a much lower tendency to crystallize, likely because the presence of the degradation products results in spatial frustration. This sample exhibits enhanced conductivity and an additional relaxation, intermediate to the ones observed in the pure sample, which likely corresponds to the noncooperative dynamics of the main degradation product. We find that dispersing the antibiotic in polylactic acid results in an amorphous sample, which does not crystallize at room temperature for relatively long times.

A thermodynamically consistent phase diagram of a trimorphic pharmaceutical, l-tyrosine ethyl ester, based on limited experimental data.

Crystalline polymorphs possess different physical properties, and phase changes between those polymorphs may affect the properties of engineered materials such as drugs. This is very well illustrated by the large effort that is put into the capability to predict phase behaviour of pharmaceuticals to avoid the unexpected appearance of different crystal forms. Much progress has been made, but one of the remaining challenges is (the accuracy in) the prediction of phase behaviour as a function of temperature. Obviously, predictions should at a certain point be verified against experimental data; however, it may not always be easy to elucidate the phase behaviour of a given compound experimentally, because thermodynamically and kinetically controlled phenomena occur in a convoluted fashion in experimental data. The present paper discusses the trimorphism of l-tyrosine ethyl ester as an example case of how experimental data in combination with the thermodynamic tenets lead to a consistent phase diagram, which can be used as the basis for pharmaceutical formulations and for comparison with polymorph predictions by computer. The positions of the two-phase equilibria I-II, I-III, and I-L have been obtained experimentally. Using the Clapeyron equation and the alternation rule, it has been shown how the positions of the other equilibria II-L, III-L, and II-III can be deduced in combination with the stability rankings of the phases and the phase equilibria. The experimental data have been obtained by synchrotron X-ray diffraction, Raman spectroscopy, and thermal analysis as a function of pressure and temperature. Furthermore, laboratory X-ray diffraction as a function of temperature and differential scanning calorimetry have been used. At room temperature, form II is the most stable phase, which remains stable with increasing pressure, as it possesses the smallest specific volume. Form I becomes stable above 33 °C (306 K), but with increasing pressure it turns into form III. On thermodynamic grounds, form III is expected to have a stable domain at very low temperatures.

Dynamic heterogeneity in an orientational glass.

The family of compounds CBrnCl4-n has been proven helpful in unraveling microscopic mechanisms responsible for glassy behavior. Some of the family members show translational ordered phases with minimal disorder which appears to reveal glassy features, thus deserving special attention in the search for universal glass anomalies. In this work, we studied CBrCl3 dynamics by performing extensive molecular dynamics simulations. Molecules of this compound perform reorientational discrete jumps, where the atoms exchange equivalent positions among each other revealing a cage-orientational jump motion fully comparable to the cage-rototranslational jump motion in supercooled liquids. Correlation times were calculated from rotational autocorrelation functions showing good agreement with previous reported dielectric results. From mean waiting and persistence times calculated directly from trajectory results, we are able to explain which microscopic mechanisms lead to characteristic times associated with α- and ß-relaxation times measured experimentally. We found that two nonequivalent groups of molecules have a longer characteristic time than the other two nonequivalent groups, both of them belonging to the asymmetric unit of the monoclinic (C2/c) lattice.

The structure of liquid water beyond the first hydration shell.

To date there is a general consensus on the structure of the first coordination shells of liquid water, namely tetrahedral short range order of molecules. In contrast, little is known about the structure at longer distances and the influence of the tetrahedral molecular arrangement of the first shells on the order at these length scales. An expansion of the distance dependent excess entropy is used in this contribution to find out which molecular arrangements are important at each distance range. This was done by splitting the excess entropy into two parts: one connected to the relative position of two molecules and the other one related to their relative orientation. A transition between two previously unknown regimes in liquid water is identified at a distance of about ∼6 Å: from a predominantly orientational order at shorter distances to a regime at larger distances of up to ∼9 Å where the order is predominantly positional and molecules are distributed with the same tetrahedral symmetry as the very first molecules.

A robust comparison of dynamical scenarios in a glass-forming liquid.

We use Bayesian inference methods to provide fresh insights into the sub-nanosecond dynamics of glycerol, a prototypical glass-forming liquid. To this end, quasielastic neutron scattering data as a function of temperature have been analyzed using a minimal set of underlying physical assumptions. On the basis of this analysis, we establish the unambiguous presence of three distinct dynamical processes in glycerol, namely, translational diffusion of the molecular centre of mass and two additional localized and temperature-independent modes. The neutron data also provide access to the characteristic length scales associated with these motions in a model-independent manner, from which we conclude that the faster (slower) localized motions probe longer (shorter) length scales. Careful Bayesian analysis of the entire scattering law favors a heterogeneous scenario for the microscopic dynamics of glycerol, where molecules undergo either the faster and longer or the slower and shorter localized motions.

An Integrated View of the Influence of Temperature, Pressure, and Humidity on the Stability of Trimorphic Cysteamine Hydrochloride.

Understanding the phase behavior of pharmaceuticals is important for dosage form development and regulatory requirements, in particular after the incident with ritonavir. In the present paper, a comprehensive study of the solid-state phase behavior of cysteamine hydrochloride used in the treatment of nephropathic cystinosis and recently granted orphan designation by the European Commission is presented employing (high-pressure) calorimetry, water vapor sorption, and X-ray diffraction as a function of temperature. A new crystal form (I2/a, form III) has been discovered, and its structure has been solved by X-ray powder diffraction, while two other crystalline forms are already known. The relative thermodynamic stabilities of the commercial form I and of the newly discovered form III have been established; they possess an overall enantiotropic phase relationship, with form I stable at room temperature and form III stable above 37 °C. Its melting temperature was found at 67.3 ± 0.5 °C. Cysteamine hydrochloride is hygroscopic and immediately forms a concentrated saturated solution in water with a surprisingly high concentration of 47.5 mol % above a relative humidity of 35%. No hydrate has been observed. A temperature-composition phase diagram is presented that has been obtained with the unary pressure-temperature phase diagram, measurements, and calculations. For development, form I would be the best form to use in any solid dosage form, which should be thoroughly protected against humidity.

Dynamic characterization of crystalline and glass phases of deuterated 1,1,2,2 tetrachloroethane.

A thorough characterization of the γ, ß, and glass phases of deuterated 1,1,2,2 tetrachloroethane (C2D2Cl4) via nuclear quadrupole resonance and Molecular Dynamic Simulations (MDSs) is reported. The presence of molecular reorientations was experimentally observed in the glass phase and in the ß phase. In the ß phase, and from MDS, these reorientations are attributed to two possible movements, i.e., a 180° reorientation around the C2 molecular symmetry axis and a reorientation of the molecule between two non-equivalent positions. In the glass phase, the spin-lattice relaxation time T1 is of the order of 16 times lower than in the crystalline phase and varies as T(-1) below 100 K in good agreement with the strong quadrupolar relaxation observed in amorphous materials and in the glassy state of molecular organic systems. The activation energy of molecular reorientations in the glass phase (19 kJ/mol) is comparable to that observed in the glassy crystal of a "molecular cousin" compound, Freon 112 (C2F2Cl4), for the secondary ß-relaxation. Moreover, the on-site orientational motion of tetrachloroethane molecules offers a new indirect evidence of the prominent role of such orientational disorder in glassy dynamics.

Colossal Reversible Barocaloric Effects in a Plastic Crystal Mediated by Lattice Vibrations and Ion Diffusion.

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 (|ΔT| ≈ 10 K) and isothermal entropy changes (|ΔS| ≈ 100 J K-1 kg-1). However, BCE typically require large pressure shifts due to irreversibility issues, and sizeable |ΔT| and |ΔS| 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 Δp ≈ 0.23 (0.10) GPa, |ΔSrev| = 280 (200) J K-1 kg-1 and |ΔTrev| = 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 |ΔS| 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.

Liquid-liquid miscibility gaps in drug-water binary systems: crystal structure and thermodynamic properties of prilocaine and the temperature-composition phase diagram of the prilocaine-water system.

EMLA cream, a "eutectic mixture of local anesthetics", was developed in the early 1980s by Astra Pharmaceutical Production. The mixture of anesthetics containing lidocaine, prilocaine, and water is liquid at room temperature, which is partly due to the eutectic equilibrium between prilocaine and lidocaine at 293 K, as was clear from the start. However, the full thermodynamic background for the stability of the liquid and its emulsion-like appearance has never been elucidated. In the present study of the binary system prilocaine-water, a region of liquid-liquid demixing has been observed, linked to a monotectic equilibrium at 302.4 K. It results in a prilocaine-rich liquid containing approximately 0.7 mol fraction of anesthetic. Similar behavior has been reported for the binary system lidocaine-water (Céolin, R.; et al. J. Pharm. Sci. 2010, 99 (6), 2756-2765). In the ternary mixture, the combination of the monotectic equilibrium and the above-mentioned eutectic equilibrium between prilocaine and lidocaine results in an anesthetic-rich liquid that remains stable below room temperature. This liquid forms an emulsion-like mixture in the presence of an aqueous solution saturated with anesthetics. Physical properties and the crystal structure of prilocaine are also reported.

Eutectic Mixture Formation and Relaxation Dynamics of Coamorphous Mixtures of Two Benzodiazepine Drugs.

The formation of coamorphous mixtures of pharmaceuticals is an interesting strategy to improve the solubility and bioavailability of drugs, while at the same time enhancing the kinetic stability of the resulting binary glass and allowing the simultaneous administration of two active principles. In this contribution, we describe kinetically stable amorphous binary mixtures of two commercial active pharmaceutical ingredients, diazepam and nordazepam, of which the latter, besides being administered as a drug on its own, is also the main active metabolite of the other in the human body. We report the eutectic equilibrium-phase diagram of the binary mixture, which is found to be characterized by an experimental eutectic composition of 0.18 molar fraction of nordazepam, with a eutectic melting point of Te = 395.4 ± 1.2 K. The two compounds are barely miscible in the crystalline phase. The mechanically obtained mixtures were melted and supercooled to study the glass-transition and molecular-relaxation dynamics of amorphous mixtures at the corresponding concentration. The glass-transition temperature was always higher than room temperature and varied linearly with composition. The Te was lower than the onset of thermal decomposition of either compound (pure nordazepam decomposes upon melting and pure diazepam well above its melting point), thus implying that the eutectic liquid and glass can be obtained without any degradation of the drugs. The eutectic glass was kinetically stable against crystallization for at least a few months. The relaxation processes of the amorphous mixtures were studied by dielectric spectroscopy, which provided evidence for a single structural (α) relaxation, a single Johari-Goldstein (ß) relaxation, and a ring-inversion conformational relaxation of the diazepinic ring, occurring on the same timescale in both drugs. We further characterized both the binary mixtures and pure compounds by FTIR spectroscopy and first-principles density functional theory (DFT) simulations to analyze intermolecular interactions. The DFT calculations confirm the presence of strong attractive forces within the heteromolecular dimer, leading to large dimer interaction energies of the order of -0.1 eV.

Amorphous solid dispersions of curcumin in a poly(ester amide): Antiplasticizing effect on the glass transition and macromolecular relaxation dynamics, and controlled release.

In order to exploit the pharmacological potential of natural bioactive molecules with low water solubility, such as curcumin, it is necessary to develop formulations, such as amorphous polymer dispersions, which allow a constant release rate and at the same time avoid possible toxicity effects of the crystalline form of the molecule under scrutiny. In this study, polymer dispersions of curcumin were obtained in PADAS, a biodegradable semicrystalline copolymer based on 1,12-dodecanediol, sebacic acid and alanine. The dispersions were fully characterized by means of differential scanning calorimetry and broadband dielectric spectroscopy, and the drug release profile was measured in a simulated body fluid. Amorphous homogeneous binary dispersions were obtained for curcumin mass fraction between 30 and 50%. Curcumin has significantly higher glass transition temperature Tg (≈ 347 K) than the polymer matrix (≈274-277 K depending on the molecular weight), and dispersions displayed Tg's intermediate between those of the pure amorphous components, implying that curcumin acts as an effective antiplasticizer for PADAS. Dielectric spectroscopy was employed to assess the relaxation dynamics of the binary dispersion with 30 wt% curcumin, as well as that of each (amorphous) component separately. The binary dispersion was characterized by a single structural relaxation, a single Johari-Goldstein process, and two local intramolecular processes, one for each component. Interestingly, the latter processes scaled with the Tg of the sample, indicating that they are viscosity-sensitive. In addition, both the pristine polymer and the dispersion exhibited an interfacial Maxwell-Wagner relaxation, likely due to spatial heterogeneities associated with phase disproportionation in this polymer. The release of curcumin from the dispersion in a simulated body fluid followed a Fickian diffusion profile, and 51% of the initial curcumin content was released in 48 h.

The Phase Diagram of the API Benzocaine and Its Highly Persistent, Metastable Crystalline Polymorphs.

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.

Immediate-sustained lactate release using alginate hydrogel assembled to proteinase K/polymer electrospun fibers.

This work proposes a microfibers-hydrogel assembled composite as delivery vehicle able to combine into a single system both burst and prolonged release of lactate. The prolonged release of lactate has been achieved by electrospinning a mixture of polylactic acid and proteinase K (26.0 mg of proteinase K and 0.99 g of PLA dissolved in 6 mL of 2:1 chloroform:acetone in the optimal case), which is a protease that catalyzes the degradation of polylactic acid into lactate. The degradation of microfibers into lactate reflects that proteinase K preserves its enzymatic activity even after the electrospinning process because of the mild operational conditions used. Besides, burst release is obtained from the lactate-loaded alginate hydrogel. The successful assembly between the lactate-loaded hydrogel and the polylactic acid/proteinase K fibers has been favored by applying a low-pressure (0.3 mbar at 300 W) oxygen plasma treatment, which transforms hydrophobic fibers into hydrophilic while the enzymatic activity is still maintained. The composite displays both fast (< 24 h) and sustained (> 10 days) lactate release, and allows the modulation of the release by adjusting either the amount of loaded lactate or the amount of active enzyme.

SbSeI and SbSeBr micro-columnar solar cells by a novel high pressure-based synthesis process.

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.