Polymerization in the solid state is generally infeasible due to restrictions on mobility. However, in this work, the solid-state photopolymerization of crystalline dicyclopentadiene is demonstrated via photoinitiated ring-opening metathesis polymerization. The source of mobility in the solid state is attributed to the plastic crystal nature of dicyclopentadiene, which yields local short-range mobility due to orientational degrees of freedom. Polymerization in the solid state enables photopatterning, volumetric additive manufacturing of free-standing structures, and fabrication with embedded components. Solid-state photopolymerization of dicyclopentadiene offers a new paradigm for advanced and freeform fabrication of high-performance thermosets.

Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.

Conformations in the solid state are typically fixed during crystallization. Transference of \"frozen\" C=C conformations in 3,5-bis((E)-2-(pyridin-4-yl)vinyl)methylbenzene (CH3-3,5-bpeb) by photodimerization selectively yielded cyclobutane and dicyclobutane isomers, one of which (Isomer 2) exhibited excellent in vitro anti-cancer activity towards T-24, 7402, MGC803, HepG-2, and HeLa cells.

During recent years there have been shortages of certain drugs due to problems in raw material supply. These are often related to active ingredients but could also affect excipients. Lactose is one of the most used excipients in tableting and comes in two anomeric and several solid-state forms. The aim of this study was to utilize lactose from a dairy side-stream and compare it against a commercial reference in direct compression. This would be a sustainable option and would secure domestic availability during crises. Two types of lactose, spray-dried and freeze-dried, were evaluated. Lactose was mixed with microcrystalline cellulose in different ratios together with lubricant and glidant, and flowability and tabletability of the formulations was characterized. The fully amorphous and small particle-sized spray-dried lactose flowed inadequately but exhibited good tabletability. The larger particle-sized, freeze-dried lactose exhibited sufficient flow and better tabletability than the commercial reference. However, disintegration and drug release were slower when using the investigational lactose formulations. This was most likely due to remaining milk proteins, especially caseins, in the lactose. Overall, the investigational lactose provides promise for the use of such a side-stream product during crisis situations but enhancing their properties and/or purity would be needed.

The concept of electronic orbitals has enabled the understanding of a wide range of physical and chemical properties of solids through the definition of, for example, chemical bonding between atoms. In the transmission electron microscope, which is one of the most used and powerful analytical tools for high-spatial-resolution analysis of solids, the accessible quantity is the local distribution of electronic states. However, the interpretation of electronic state maps at atomic resolution in terms of electronic orbitals is far from obvious, not always possible, and often remains a major hurdle preventing a better understanding of the properties of the system of interest. In this review, the current state of the art of the experimental aspects for electronic state mapping and its interpretation as electronic orbitals is presented, considering approaches that rely on elastic and inelastic scattering, in real and reciprocal spaces. This work goes beyond resolving spectral variations between adjacent atomic columns, as it aims at providing deeper information about, for example, the spatial or momentum distributions of the states involved. The advantages and disadvantages of existing experimental approaches are discussed, while the challenges to overcome and future perspectives are explored in an effort to establish the current state of knowledge in this field. The aims of this review are also to foster the interest of the scientific community and to trigger a global effort to further enhance the current analytical capabilities of transmission electron microscopy for chemical bonding and electronic structure analysis.

Responsive organic luminescent aggregates have a wide range of application fields, but currently there is still a lack of reasonable molecular design strategies. Introducing ion-π interactions into molecules can effectively alter their luminescent properties. However, current research typically focuses on ion localization at luminescent conjugated groups with the strong interaction forces. In this work, we introduce the flexible alkoxy chain spacers between fluorescent conjugated groups and ion-π interaction sites, and then adjust the fluorescence performance of the molecule by changing the strength of ion-π interactions. Bromine ion-based molecules with strong ion-π interactions exhibit high and stable fluorescence quantum yields in crystals and amorphous powders under the external stimuli. Hexafluorophosphate ion-based molecules with weak ion-π interactions have the high fluorescence quantum yield in crystals and very low fluorescence quantum yield in amorphous powders, showing variable fluorescence intensities under external stimuli. This demonstrates a new class of responsive organic luminescent solid-state materials.

BACKGROUND: The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms. This study provides a significant contribution to understanding bilastine\'s polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products.
METHODS: The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 +  + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

In this study, we demonstrate the feasibility of rapid volumetric additive manufacturing in the solid state. This additive manufacturing technology is particularly useful in outer space missions (microgravity) and/or for harsh environment (e.g., on ships and vehicles during maneuvering, or on airplanes during flight). A special thermal gel is applied here to demonstrate the concept, that is, ultraviolet crosslinking in the solid state. The produced hydrogels are characterized and the water-content-dependent heating/cooling/water-responsive shape memory effect is revealed. Here, the shape memory feature is required to eliminate the deformation induced in the process of removing the uncrosslinked part from the crosslinked part in the last step of this additive manufacturing process.

Octreotide acetate, the active pharmaceutical ingredient in the long-acting release (LAR) drug product Sandostatin®, is a cyclic octapeptide that mimics the naturally occurring somatostatin peptide hormone. Modern NMR can be a robust analytical method to identify and quantify octreotide molecules. Previous 1H chemical shift assignments were mostly performed in organic solvents, and no assignments for heteronuclear 13C, 15N, and aromatic 1H nuclei are available. Here, using state-of-the-art 1D and 2D homo- and heteronuclear NMR experiments, octreotide was fully assigned, including water exchangeable amide protons, in aqueous buffer except for 13CO and 15NH of F1, 15NH of C2, and 15NζHζ of K5 that were not observed because of water exchange or conformational exchange. The solution NMR spectra were then directly compared with 1D 1H/13C/15N solid-state NMR (SSNMR) spectra showing the potential applicability of 13C/15N SSNMR for octreotide drug product characterization.

This review discusses the entire progress made on the anthelmintic drug praziquantel, focusing on the solid state and, therefore, on anhydrous crystalline polymorphs, amorphous forms, and multicomponent systems (i.e., hydrates, solvates, and cocrystals). Despite having been extensively studied over the last 50 years, new polymorphs and the greater part of their cocrystals have only been identified in the past decade. Progress in crystal engineering science (e.g., the use of mechanochemistry as a solid form screening tool and more strategic structure-based methods), along with the development of analytical techniques, including Synchrotron X-ray analyses, spectroscopy, and microscopy, have furthered the identification of unknown crystal structures of the drug. Also, computational modeling has significantly contributed to the prediction and design of new cocrystals by considering structural conformations and interactions energy. Whilst the insights on praziquantel polymorphs discussed in the present review will give a significant contribution to controlling their formation during manufacturing and drug formulation, the detailed multicomponent forms will help in designing and implementing future praziquantel-based functional materials. The latter will hopefully overcome praziquantel\'s numerous drawbacks and exploit its potential in the field of neglected tropical diseases.