Polymorphism of Sildenafil: A New Metastable Desolvate

A new anhydrous polymorph of the free base of sildenafil and two solvates (acetonitrile and propanenitrile) have been discovered and fully characterized. The new polymorph can be considered a desolvate of the acetonitrile solvate and is related to the most stable form I by morphotropism. The new polymorph can only be obtained by desolvation of the acetonitrile solvate. Thus, this study is a new example of the importance of this multicomponent family of solid forms in the discovery of new polymorphs of active pharmaceutical ingredients

Morphotropism and 'Quasi-Isostructurality' in the Three High Z′ Concomitant Polymorphs of Efinaconazole

The crystal structures of the three efinaconazole anhydrous forms have been solved by single-crystal X-ray diffraction showing a very rare case of nearly isostructural polymorphism. The analysis of their crystal structures revealed that forms I and III are 'quasi-isostructural' polymorphs and are morphotropically related to form II. The identical conformational and supramolecular environment can explain the concomitant polymorphism phenomenon observed for this important active pharmaceutical ingredient

Cooperativity effects in a new pterostilbene/phenanthroline cocrystal

The SCXRD structure of the natural dietary compound pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) and phenanthroline (1,10-phenanthroline) cocrystal is reported herein. In the solid state the cocrystal forms several H-bonded and Csingle bondH···π supramolecular synthons that have been analyzed by DFT calculations, with a particular focus on the parallel face-to-face stacking of the phenanthroline rings, a relevant and quite unusual feature (antiparallel displaced mode is more common). Cooperativity effects between H-bonding and aromatic interactions have been studied to rationalize the formation of this unusual π-stacking mode and the supramolecular assemblies have been further analyzed using several computational techniques, i.e., molecular electrostatic potential (MEP) surfaces and the quantum theory of 'atom-in-molecules' (QTAIM) combined with reduced density gradient (RDG) plots

Alternativas para el aprovechamiento de los residuos de poda del arbolado urbano de Valledupar según su impacto en el inventario del ciclo de vida

Valledupar es admirado por sus visitantes no solo por su música y el festival de la leyenda vallenata, sino también por el verde de sus árboles presentes en sus calles, avenidas y los frentes de las viviendas. Se estima que la ciudad cuenta con más de 70.000 árboles donde la gran mayoría de sus especies con nombres comunes como: árbol de Mango, Caucho y Uva Venezolana entre otros. La generación y gestión de residuos urbanos es considerado un problema global crítico, y un problema medioambiental frecuentemente no reconocido que gira en torno a la generación de residuos urbanos, afectando también a la ciudad de Valledupar. En el presente estudio se busca elaborar el análisis entre algunas alternativas de transformación de residuos de poda del arbolado urbano de Valledupar mediante la Evaluación del Ciclo de Vida de cada uno de los procesos de transformación dispuestos en esta investigación, con la finalidad de proponer una estrategia que aporte al desarrollo sostenible, cuidado del medio ambiente y bienestar social de la comunidad. Obteniendo así la información necesaria para identificar problemáticas e impactos ambientales, para de esta manera analizar la información de alternativas de gestión existentes, y de igual forma evaluar el ciclo de vida y cada uno de los procesos identificados, mediante una metodología aplicada de análisis de datos a cada uno de los procesos propuestos para la transformación de residuos de poda del arbolado de Valledupar, llegando así aplicar un análisis de ciclo de vida (ACV), con la utilización del software OPENLCA.MaestríaMagister en Ingeniería Ambienta

Derisking Development by a Cocrystallization Screen of a Novel Selective Inhaled JAK-STAT inhibitor

The discovery and detailed characterization of several new solid forms of a novel selective inhaled JAK-STAT inhibitor are described. Using a holistic cocrystallization screen approach to explore its formulation landscape, we decrease the risk of future potential development failures due to a nonoptimal pharmacokinetic lung profile or undesired lung effects in humans

Revision of the Crystal structure of the orthorhombic polymorph of oxyma: on the importance of π-hole interactions and their interplay with H-bonds

In this work the crystal structure of the previously described orthorhombic polymorph of the coupling reagent Oxyma has been revised, corrected now as centrosymmetric and analyzed by means of DFT calculations. In the solid state the structure forms a network of H-bonds and self-assembled dimers that are held together by the formation of N···C π-hole interactions involving the C-atom of the imino group. The H-bonding and π-hole interactions observed in the solid state were rationalized using molecular electrostatic potential (MEP) surfaces, focusing on the H-bond donor-acceptor groups and the π-hole observed above and below the molecular plane. The interactions and their interplay have been characterized by using two methodologies based on the topology of the electron density, which are the quantum theory of 'atom-in-molecules' (QTAIM) and the noncovalent interaction plot (NCIplot)

Hydrogen bonding versus π-interactions: their key competition in sildenafil solvates

Herein we report the X-ray characterization of four sildenafil solvates where the conformation of the pyrazolo[3,4-d]pyrimidine and phenyl rings depends on the solvent. It conditions the formation of an apparently innocent intramolecular H-bond that has a remarkable influence on the solid state architecture of the sildenafil solvates. DFT calculations indicate that a delicate balance between the energies of H-bonding and π-π (or lp-π) interactions are crucial

Crystal engineering of nutraceutical phytosterols: new cocrystal solid solutions?

A cocrystal screening conducted with solid solutions of three phytosterols (β-sitosterol, campesterol and stigmasterol) and a set of coformers with strong hydrogen bond donors reveals that multicomponent solid solutions are preferentially formed instead of pure cocrystals and are much enriched with β-sitosterol with respect to stigmasterol, a natural product with cytotoxicity concerns

Synthesis and characterization of a new norfloxacin/resorcinol cocrystal with enhanced solubility and dissolution profile

A new cocrystal of Norfloxacin, a poorly soluble fluoroquinolone antibiotic, has been synthetized by a solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. The new cocrystal exists in both anhydrous and monohydrate forms with the same (1:1) Norfloxacin/resorcinol stoichiometry. The solubility of Norfloxacin and the hydrated cocrystal were determined by the shake-flask method. While Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, the cocrystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher. The dissolution rate was tested at four biorelevant pH levels of the gastrointestinal tract: 2.0, 4.0, 5.5, and 7.4. In a first set of comparative tests, the dissolution rate of Norfloxacin and the cocrystal was determined separately at each pH value. Both solid forms showed the highest dissolution rate at pH 2.0, where Norfloxacin is totally protonated. Then, the dissolution rate decreases as pH increases. In a second set of experiments, the dissolution of the cocrystal was evaluated by a unique dissolution test, in which the pH dynamically changed from 2.0 to 7.4, stepping 30 min at each of the four biorelevant pH values. Results were quite different in this case, since dissolution at pH 2 affects the behavior of Norfloxacin at the rest of the pH values

Two New Polymorphic Cocrystals of Zafirlukast: Preparation, Crystal Structure, and Stability Relations

Two new cocrystals of zafirlukast with piperazine, existing in five different solid forms, have been discovered during a cocrystal screening. The crystal structure of one of these forms has been determined by single crystal X-ray diffraction, and the stability landscape of the crystalline forms of the new cocrystal has been studied. In the present article, we extend the knowledge about the solid state of this important pharmaceutical drug for the treatment of asthma by reporting the crystal structures of two new solvates (acetonitrile and butanol) and the elusive anhydrous Form X, which have been solved by single crystal X-ray diffraction