scholarly journals Application of 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide as Coformer in Formation of Pharmaceutical Cocrystals

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 359 ◽  
Author(s):  
Aneta Wróblewska ◽  
Justyna Śniechowska ◽  
Sławomir Kaźmierski ◽  
Ewelina Wielgus ◽  
Grzegorz D. Bujacz ◽  
...  
Keyword(s):  
Solid State Nmr ◽  
Ball Mill ◽  
Barbituric Acid ◽  
Crystal Packing ◽  
Thiobarbituric Acid ◽  
Active Pharmaceutical Ingredients ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Tautomeric Forms ◽  
Biological Studies

Two, well defined binary crystals with 1-Hydroxy-4,5-Dimethyl-Imidazole 3-Oxide (HIMO) as coformer and thiobarbituric acid (TBA) as well barbituric acid (BA) as Active Pharmaceutical Ingredients (APIs) were obtained by cocrystallization (from methanol) or mechanochemically by grinding. The progress of cocrystal formation in a ball mill was monitored by means of high-resolution, solid state NMR spectroscopy. The 13C CP/MAS, 15N CP/MAS and 1H Very Fast (VF) MAS NMR procedures were employed to inspect the tautomeric forms of the APIs, structure elucidation of the coformer and the obtained cocrystals. Single crystal X-ray studies allowed us to define the molecular structure and crystal packing for the coformer as well as the TBA/HIMO and BA/HIMO cocrystals. The intermolecular hydrogen bonding, π–π interactions and CH-π contacts responsible for higher order organization of supramolecular structures were determined. Biological studies of HIMO and the obtained cocrystals suggest that these complexes are not cytotoxic and can potentially be considered as therapeutic materials.

scholarly journals Assay and physicochemical characterization of the antiparasitic albendazole

2012 ◽  
Vol 48 (2) ◽  
pp. 281-290 ◽  
Author(s):  
Noely Camila Tavares Cavalcanti ◽  
Giovana Damasceno Sousa ◽  
Maria Alice Maciel Tabosa ◽  
José Lamartine Soares Sobrinho ◽  
Leila Bastos Leal ◽  
...  
Keyword(s):  
Physicochemical Characterization ◽  
Analytical Techniques ◽  
Assay Method ◽  
Active Pharmaceutical Ingredients ◽  
X Ray Diffraction ◽  
Melting Points ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Complementary Techniques

The aim of this study was to characterize three batches of albendazole by pharmacopeial and complementary analytical techniques in order to establish more detailed specifications for the development of pharmaceutical forms. The ABZ01, ABZ02, and ABZ03 batches had melting points of 208 ºC, 208 ºC, and 209 ºC, respectively. X-ray diffraction revealed that all three batches showed crystalline behavior and the absence of polymorphism. Scanning electron microscopy showed that all the samples were crystals of different sizes with a strong tendency to aggregate. The samples were insoluble in water (5.07, 4.27, and 4.52 mg mL-1, respectively) and very slightly soluble in 0.1 M HCl (55.10, 56.90, and 61.70 mg mL-1, respectively) and additionally showed purities within the range specified by the Brazilian Pharmacopoeia 5th edition (F. Bras. V; 98% to 102%). The pharmacopeial assay method was not reproducible and some changes were necessary. The method was validated and showed to be selective, specific, linear, robust, precise, and accurate. From this characterization, we concluded that pharmacopeial techniques alone are not able to detect subtle differences in active pharmaceutical ingredients; therefore, the use of other complementary techniques is required to ensure strict quality control in the pharmaceutical industry.

35Cl solid-state NMR of HCl salts of active pharmaceutical ingredients: structural prediction, spectral fingerprinting and polymorph recognition

CrystEngComm ◽  
2014 ◽  
Vol 16 (31) ◽  
pp. 7334-7356 ◽  
Author(s):  
Marcel Hildebrand ◽  
Hiyam Hamaed ◽  
Andrew M. Namespetra ◽  
John M. Donohue ◽  
Riqiang Fu ◽  
...  
Keyword(s):  
Solid State ◽  
Plane Wave ◽  
Dft Calculations ◽  
First Principles ◽  
Solid State Nmr ◽  
Active Pharmaceutical Ingredients ◽  
Structural Prediction ◽  
Pharmaceutical Ingredients

A series of HCl salts of active pharmaceutical ingredients (APIs) have been characterized via35Cl solid-state NMR (SSNMR) spectroscopy and first-principles plane-wave DFT calculations of 35Cl NMR interaction tensors.

scholarly journals Structural motifs in salts of sulfathiazole: implications for design of salt forms in pharmaceuticals APIs

CrystEngComm ◽  
2018 ◽  
Vol 20 (24) ◽  
pp. 3428-3434
Author(s):  
Colin C. Seaton ◽  
Rayan R. Thomas ◽  
Eman A. A. Essifaow ◽  
Elisa Nauha ◽  
Tasnim Munshi ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Crystal Packing ◽  
Active Pharmaceutical Ingredients ◽  
Structural Motifs ◽  
Pharmaceutical Ingredients ◽  
The Creation ◽  
Salt Forms

The creation of salts is a frequently used approach to modify physicochemical properties of active pharmaceutical ingredients. This work prepares a collection of sulfathiazole salts to probe the influence of counterion structure on crystal packing.

Solid-State NMR, X-Ray Diffraction, and Theoretical Studies of Neutral Mononuclear Molecular Bis(triphenylphosphine)silver(I) Mono-Carboxylate and -Nitrate Systems

2020 ◽  
Vol 73 (6) ◽  
pp. 556
Author(s):  
Simon Grabowsky ◽  
Allan H. White ◽  
Peter C. Healy ◽  
Kim M. Lapere ◽  
Seik Weng Ng ◽  
...  
Keyword(s):  
Solid State ◽  
Solid State Nmr ◽  
Crystal Packing ◽  
Computational Modelling ◽  
Inverse Correlation ◽  
X Ray Diffraction ◽  
Weakly Bound ◽  
X Ray ◽  
Nmr Study ◽  
Structure Determinations

Neutral mononuclear molecular silver(i) carboxylate complexes of the form [(Ph3P)2Ag(O2XY)] with O2XY=O2CCH2Ph, O2CCHPh2, O2CC(CH3)3, O2CCH2C(CH3)3, and O2CCF3 (compounds 1–4 and 5β) have been investigated in the solid state using single-crystal X-ray structure determinations, 1D 31P CPMAS NMR and 2D 31P–31P CPCOSY NMR measurements, and ab initio computational modelling. The results show that these complexes contain P2AgO2 molecular cores with four-coordinate silver in which the carboxylate ligands are weakly bound to the silver atoms via the two oxygen atoms giving rise to unsymmetrical chelate units. Crystal structure determinations and solid-state NMR spectra have also been analysed for the mononuclear molecular silver(i) nitrate complex [(Ph3P)2Ag(O2NO)] (9α) and two polymorphs of its toluene monosolvate (11α, β). In 9α, the two PPh3 ligands are of the same chirality, whereas in 11α, β, they are opposed. The crystalline environments in the polymorphs have been explored by way of Hirshfeld surface analyses, after quantum-mechanical isolated-molecule calculations had shown that although the molecular energies of the experimental geometries of 9α, and 11α, β are significantly different from each other and from the energies of the optimized geometries, the latter, in contrast, do not differ significantly from each other despite the conformational isomerism. It has further been shown using 9α as an example that the energy dependence on variation of the P–Ag–P angle over a range of ~15° is only ~5 kJ mol−1. All this indicates that the forces arising from crystal packing result in significant perturbations in the experimental geometries, but do not alter the stereoisomerism caused by the donor atom array around the Ag atom. In the NMR study, a strong inverse correlation has been found between 1J(107/109Ag,31P) and the Ag–P bond length across all carboxylate and nitrate compounds.

scholarly journals Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

Crystals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1088
Author(s):  
Cristóbal Verdugo-Escamilla ◽  
Carolina Alarcón-Payer ◽  
Antonio Frontera ◽  
Francisco Javier Acebedo-Martínez ◽  
Alicia Domínguez-Martín ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Intermolecular Forces ◽  
Active Pharmaceutical Ingredients ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Great Stability ◽  
X Ray ◽  
Pharmaceutical Ingredients ◽  
Interesting Approach ◽  
Pharmaceutical Materials

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.

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