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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pharmaceutical paroxetine-based organic salts of carboxylic acids with optimized properties: the identification and characterization of potential novel API solid forms

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Author(s):
Carvalho, Jr., Paulo S. [1] ; Diniz, Luan F. [2] ; Tenorio, Juan C. [2] ; Souza, Matheus S. [2] ; Franco, Chris H. J. [3] ; Rial, Rafael C. [1] ; Warszawski de Oliveira, Karla Regina [1] ; Nazario, Carlos E. D. [1] ; Ellena, Javier [2]
Total Authors: 9
Affiliation:
[1] Univ Fed Mato Grosso do Sul, Inst Quim, BR-79074460 Campo Grande, MS - Brazil
[2] Univ Sao Paulo, Inst Fis Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil
[3] Univ Fed Juiz de Fora, Dept Quim, BR-36036900 Juiz De Fora, MG - Brazil
Total Affiliations: 3
Document type: Journal article
Source: CrystEngComm; v. 21, n. 24, p. 3668-3678, JUN 28 2019.
Web of Science Citations: 3
Abstract

Paroxetine hydrochloride, PRX HCl, is an important and widely prescribed antidepressant drug for anxiety and depression treatment. Since hydrochloride salts can cause problems in their manufacture, we have designed organic salts with oxalic, fumaric, maleic and l-tartaric acids based on the NH2+MIDLINE HORIZONTAL ELLIPSISCOO- synthon. All the salts were obtained from an innovative anion exchange method: selective crystallization from a mixture of PRX HCl and an acid in a certain ratio. The crystal structures of paroxetine (PRX) salts with dicarboxylic acids were determined by the single-crystal X-ray diffraction (SCXRD) method and were also analysed by thermogravimetric analysis, differential scanning calorimetry and FT-IR spectroscopy. Except for FUM and MAL acids, all the carboxylic acids form hydrate salts. Oxalate and tartrate salts are formed through the complete protonation of the anion and exhibit a 1 : 2 stoichiometry. All structures have a Z ` > 1 and different conformations are found for the PRX molecules. In general, the ionic units in the salts extend into chains that pack cohesively, via CHMIDLINE HORIZONTAL ELLIPSISO and CHMIDLINE HORIZONTAL ELLIPSIS pi interactions, into layers. The oxalate salt forms a channel structure where H2O molecules are hosted. On the other hand, the presence of water molecules in the tartrate salt allows the packing of ionic layers. The organic salts are thermally more stable than the commercial PRX form, m.p. > 143 degrees C. They exhibit lower solubility compared to the hydrochloride form. The scientific contributions of this study show the diversity of the PRX solid forms and identify candidates for use in new antidepressant API solid formulations. (AU)

FAPESP's process: 16/08823-4 - Electron Density Studies of Antiretroviral Drugs as a tool for the Design of New Solid Phases.
Grantee:Juan Carlos Tenorio Clavijo
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 12/05616-7 - Solid-state characterization of anticonvulsant and antidepressant phamaceutical compounds: Design of new crystal forms.
Grantee:Paulo de Sousa Carvalho Júnior
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/25694-0 - Obtaining, characterization and evaluation of novel crystalline solid forms of drugs used treatment of tuberculosis
Grantee:Luan Farinelli Diniz
Support Opportunities: Scholarships in Brazil - Master