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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CrystEngComm; v. 21, n. 24, p. 3668-3678, JUN 28 2019.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 16/08823-4 - Estudos de Densidade Eletrônica de Fármacos Antirretrovirais como uma ferramenta para o Desenho de Novas Fases Sólidas.
• Beneficiário: Juan Carlos Tenorio Clavijo
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 12/05616-7 - Caracterização no estado sólido de fármacos de ação anti-convulsionantes e antidepressivos: Planejamento de novas formas cristalinas.
• Beneficiário: Paulo de Sousa Carvalho Júnior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/25694-0 - Obtenção, caracterização e avaliação de novas formas sólidas cristalinas de fármacos usados no tratamento da tuberculose
• Beneficiário: Luan Farinelli Diniz
• Modalidade de apoio: Bolsas no Brasil - Mestrado