Crystal forms of the hydrogen oxalate salt of o-desmethylvenlafaxine†

Dichiarante, Elena; Curzi, Marco; Giaffreda, Stefano Luca; Grepioni, Fabrizia; Maini, Lucia; Braga, Dario

doi:10.1111/jphp.12378

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…Many different approaches exist which all aim at generating different processing pathways for finding new polymorphs. Bulk crystallization experiments employ seeding, different solvents, ,, degree of saturation, and varying temperature, among others, to enable the production of new polymorphs which in other terms just represent the fact that the energy landscape is screened . Even the usage of structure prediction methods is becoming more important as potential new polymorphs might be more easily accessible in-silico but with the prediction rate exhausting physical capabilities. ,− …”

Section: Introductionmentioning

confidence: 99%

Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration

Schrode

Bodák²,

Riegler³

et al. 2017

ACS Omega

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Solubility enhancement and thus higher bioavailability are of great importance and a constant challenge in pharmaceutical research whereby polymorph screening and selection is one of the most important tasks. A very promising approach for polymorph screening is solvent vapor annealing where a sample is exposed to an atmosphere saturated with molecules of a specific chemical/solvent. In this work, amorphous carbamazepine thin films were prepared by spin coating, and the transformation into crystalline forms under exposure to solvent vapors was investigated. Employing grazing incidence X-ray diffraction, four distinct carbamazepine polymorphs, a solvate, and hydrates could be identified, while optical microscopy showed mainly spherulitic morphologies. In vitro dissolution experiments revealed different carbamazepine release from the various thin-film samples containing distinct polymorphic compositions: heat treatment of amorphous samples at 80 °C results in an immediate release; samples exposed to EtOH vapors show a drug release about 5 times slower than this immediate one; and all the others had intermediate release profiles. Noteworthy, even the sample of slowest release has a manifold faster release compared to a standard powder sample demonstrating the capabilities of thin-film preparation for faster drug release in general. Despite the small number of samples in this screening experiment, the results clearly show how solvent vapor annealing can assist in identifying potential polymorphs and allows for estimating their impact on properties like bioavailability.

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Section: Introductionmentioning

confidence: 99%

Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration

Schrode

Bodák²,

Riegler³

et al. 2017

ACS Omega

View full text Add to dashboard Cite

show abstract

“…In the pharmaceutical industry, the polymorphic form of a drug shall be easily produced, compatible with the excipients used in the drug product manufacturing process, and remain unchanged for the duration of the drug’s shelf life. − Consequently, many designs of experiments and screening methods are applied to generate potentially the best-suited approaches and stable polymorphs. In bulk crystallization experiments, various strategies are employed, including different solvents, , seeding, degrees of saturation, varying temperature, process parameter variation, and so on. We report for the first time in psilocybin synthesis a metastable crystallization zone and a drying process that produces a single stable anhydrous polymorphic form.…”

Section: Resultsmentioning

confidence: 99%

Psilocybin: Characterization of the Metastable Zone Width (MSZW), Control of Anhydrous Polymorphs, and Particle Size Distribution (PSD)

et al. 2022

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Psilocybin, a serotonergic agonist, was granted a "breakthrough therapy" status by the Food and Drug Administration for clinical trials involving major depressive disorder and treatment-resistant depression. The direct phosphorylation of psilocin to psilocybin that uses a fast crystallization associated with a kinetically controlled process resulted in a smaller particle size distribution. Herein, the measurement of the metastable zone width (MSZW) and nucleation induction enabled a thermodynamically controlled crystallization process, which leads to the formation of a crystal structure with stronger interactions, controlled particle size distribution (PSD), and improved impurity profile. Employing a high-resolution inline microscopy viewer allowed the realtime monitoring of the crystallization process and the measurement of the particle size. We also present a comprehensive study of the formation of polymorph B (trihydrate), polymorph A (anhydrate), and polymorph H (anhydrate) using water recrystallization, which indicates that the formation of polymorph B (trihydrate) is independent of the crystallization method. However, polymorphs A and H are dependent on the mode of drying: drying at room temperature under vacuum gives rise to mainly polymorph A, and when heated even at relatively low temperatures, a mixture of polymorphs A and H beings to form.

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“…As a result, two polymorphic forms were described, and the crystal structure resolution of Form B showed that it contained hydrogen oxalate anions [4]. In spite of the low incidence of oxalic acid in the list of the most used anions in APIs [5], many other examples have also been described in the literature exhibiting the interest of the scientific community for this coformer [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Oxalic Acid, a Versatile Coformer for Multicomponent Forms with 9-Ethyladenine

et al. 2022

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Six new multicomponent solids of 9-ethyladenine and oxalic acid have been detected and characterized. The salt screening has been performed by mechanochemical and solvent crystallization processes. Single crystals of the anhydrous salts in 1:1 and 2:1 nucleobase:coformer molar ratio were obtained by solution crystallization and elucidated by single-crystal X-ray analysis. The supramolecular interactions observed in these solids have been studied using density functional theory (DFT) calculations and characterized by the quantum theory of “atoms in molecules” (QTAIM) and the noncovalent interaction plot (NCIPlot) index methods. The energies of the H-bonding networks observed in the solid state of the anhydrous salts in 1:1 and 2:1 nucleobase:coformer are reported, disclosing the strong nature of the charge assisted NH···O hydrogen bonds and also the relative importance of ancillary C–H··O H-bonds.

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Crystal forms of the hydrogen oxalate salt of o-desmethylvenlafaxine†

Abstract: Comparative solubility tests on ODV-OX Form 1 and o-desmethylvenlafaxine succinate evidenced a significant increase in solubility for the hydrogen oxalate salt (142 g/l) with respect to the succinate salt (70 g/l).

Cited by 4 publications

References 18 publications

Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration

Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration

Psilocybin: Characterization of the Metastable Zone Width (MSZW), Control of Anhydrous Polymorphs, and Particle Size Distribution (PSD)

Oxalic Acid, a Versatile Coformer for Multicomponent Forms with 9-Ethyladenine

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