Solid State Investigation and Characterization of a Nepadutant Precursor: Polymorphic and Pseudopolymorphic Forms of MEN11282

MEN11282 (<b>1</b>) is a precursor of nepadutant (MEN11420), a potent and selective antagonist at the human tachykinin NK-2 receptor (hNK-2), that has been evaluated in clinical trials for different therapeutic indications. Three crystalline forms of <b>1</b> were identified and characterized by both single crystal and powder X-ray diffraction (SCXRD and XRPD): a monohydrate (<b>1</b>·<b>H</b>_<b>2</b><b>O</b>, SCXRD) and two different anhydrous forms, namely, <b>1_α</b> and <b>1_β</b> (XRPD). Because of the relevance that the solid form of a substance of pharmaceutical interest plays during the manufacturing process, variable temperature powder X-ray diffraction (VT-XRPD) in conjunction with differential scanning calorimetry were used to investigate the behavior of the different solid forms of <b>1</b>. The rationale for the dehydration and hydration process involving <b>1·H</b>_<b>2</b><b>O</b> and <b>1_α</b> and the stability of <b>1_β</b> toward water uptake is provided based on their crystal packings

Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Four lidocaine molecular salts of dicarboxylic acids (oxalic, fumaric, malonic, and succinic) were synthesized and characterized by a combined use of X-ray powder and single-crystal diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and solid-state NMR (1H MAS and CRAMPS, and 13C and 15N CPMAS): all molecular salts show a dramatic increase in their melting point with respect to both lidocaine and lidocaine hydrochloride, and a higher dissolution rate and thermodynamic solubility in physiological solution with respect to the free base

Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Four lidocaine molecular salts of dicarboxylic acids (oxalic, fumaric, malonic, and succinic) were synthesized and characterized by a combined use of X-ray powder and single-crystal diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and solid-state NMR (1H MAS and CRAMPS, and 13C and 15N CPMAS): all molecular salts show a dramatic increase in their melting point with respect to both lidocaine and lidocaine hydrochloride, and a higher dissolution rate and thermodynamic solubility in physiological solution with respect to the free base

Folic Acid in the Solid State: A Synergistic Computational, Spectroscopic, and Structural Approach

The structure of folic acid dihydrate has been investigated in the solid state by means of a synergistic approach combining Raman spectroscopy, X-ray powder diffraction, and cutting-edge calculation methods. The comparison of the computed and measured Raman spectra was used to support the finding of a new crystalline form. Crystalline folic acid·2H2O has also been used in the preparation, via solvent free methods, of amorphous multicomponent materials and salts by reacting folic acid with LiOH, NaOH, Na2CO3, and Ca­(OH)2, which were also investigated by X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, and intrinsic dissolution rate, and this has been compared with the values of the native vitamin. The preparation and characterization of the amorphous, hydrated adduct with LiCl is also reported

Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Four lidocaine molecular salts of dicarboxylic acids (oxalic, fumaric, malonic, and succinic) were synthesized and characterized by a combined use of X-ray powder and single-crystal diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and solid-state NMR (¹H MAS and CRAMPS, and ¹³C and ¹⁵N CPMAS): all molecular salts show a dramatic increase in their melting point with respect to both lidocaine and lidocaine hydrochloride, and a higher dissolution rate and thermodynamic solubility in physiological solution with respect to the free base

Molecular Salts of Anesthetic Lidocaine with Dicarboxylic Acids: Solid-State Properties and a Combined Structural and Spectroscopic Study

Four lidocaine molecular salts of dicarboxylic acids (oxalic, fumaric, malonic, and succinic) were synthesized and characterized by a combined use of X-ray powder and single-crystal diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and solid-state NMR (¹H MAS and CRAMPS, and ¹³C and ¹⁵N CPMAS): all molecular salts show a dramatic increase in their melting point with respect to both lidocaine and lidocaine hydrochloride, and a higher dissolution rate and thermodynamic solubility in physiological solution with respect to the free base

Similar but Different: The Case of Metoprolol Tartrate and Succinate Salts

The solid-state structure and behavior of tartrate (MT-o) and succinate (MS-m) metoprolol salts have been studied with a combined experimental (X-ray diffraction by both single crystal and microcrystalline powder and differential scanning calorimetry) and modeling approach (molecular dynamics and molecular orbital calculations). In spite of their close similarity at the molecular level in the corresponding crystal lattices, calorimetric data suggest for MS-m a slightly greater cohesive energy. In addition and more importantly, they show significantly different “macroscopic” behaviors: MS-m undergoes a reversible anisotropic lattice expansion/contraction upon temperature change and once melted quickly recrystallizes to the starting crystal phase. On the other hand, MT-o expands/contracts isotropically, and upon cooling from the melt gives an amorphous solid, which, at ambient conditions, takes 6 days to completely revert to the starting crystal form. Both findings are relevant in the field of the pharmaceutical drug development; i.e., when the phase purity of these active pharmaceutical ingredients is assessed, discussed, and possibly related to drug product formulations and manufacturing methods

Molecular-Level Investigation of Hydrate–Anhydrous Phase Transformations of the Dapsone Structurally Related Compound 3,3′-Diaminophenyl Sulfone

The solid state of a novel hydrate form of 3,3′-diaminophenyl sulfone (3APS_0.5H2Oo) as well as its temperature-induced phase transitions is reported. On increasing the temperature, first a partial dehydration occurs, leading to the partially hydrated 3APS_0.1H2Oo, which then transforms into the monoclinic anhydrous form, 3APS_Am. Finally, by recrystallization of the melt 3APS_Am, a second anhydrous orthorhombic phase is obtained (3APS_Ao). This last phase transforms in 3APS_Am at a temperature between 360 and 400 K. XRD, DSC, TGA, HSM, and in silico data have been used to better understand the dehydration mechanism. With the same aim, hydration/dehydration tests have been carried out. Finally, the dehydration behavior of 3APS_0.5H2O has been discussed in comparison with that of the dapsone hydrated phase 4APS_0.33H2Om