Unexpected solvent impact in the crystallinity of praziquantel/poly (vinylpyrrolidone) formulations. A solubility, DSC and solid-state NMR study

The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The presence of PVP improves the solubility of PZQ (0.31 ± 0.01 mg/mL). A maxi...

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Detalhes bibliográficos
Autores: Costa, Emanuel D., Priotti, Josefina, Orlandi, Silvina, Leonardi, Darío, Lamas, Maria Celina, Nunes, Teresa G., Diogo, Hermínio P., Salomon, Claudio Javier, Ferreira, M. João
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2016
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/52670
Acesso em linha:http://hdl.handle.net/11336/52670
Access Level:Acceso aberto
Palavra-chave:DSC
PHARMACEUTICAL FORMULATIONS
POLY(VINYLPYRROLIDONE)
PRAZIQUANTEL
SOLID-STATE NMR
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descrição
Resumo:The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The presence of PVP improves the solubility of PZQ (0.31 ± 0.01 mg/mL). A maximum of 1.29 ± 0.03 mg/mL of PZQ in solution was achieved for the 3:1 SD (E/E). The amount of PZQ in solution depends on the amount of polymer and on the preparation method. Solid-state NMR (ssNMR) and DSC were used to understand this behavior. Results show that PMs are a mixture of crystalline PZQ with the polymer, while SDs show different degrees of drug amorphization depending on the solvent used. For E/W SDs, PZQ exists in amorphous and crystalline states, with no clear correlation between the amount of crystalline PZQ and the amount of PVP. For E/E SDs, formulations with a higher percentage of PZQ are amorphous with the components miscible in domains larger than 3 nm (1H ssNMR relaxation measurements). Albeit its higher saturation solubility, the 3:1 E/E PVP:PZQ sample has a significant crystalline content, probably due to the water introduced by the polymer. High PVP content and small crystal size account for this result.