title: Unexpected solvent impact in the crystallinity of praziquantel/poly(vinylpyrrolidone) formulations. A solubility, DSC and solid-state NMR study.
abstract: 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±0.01mg/mL). A maximum of 1.29±0.03mg/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 3nm ((1)H 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.
authors: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: Emanuel D
authors: ED
authors: Costa
authors: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors: Josefina
authors: J
authors: Priotti
authors: Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors: Silvina
authors: S
authors: Orlandi
authors: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors: Darío
authors: D
authors: Leonardi
authors: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors: María C
authors: MC
authors: Lamas
authors: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: Teresa G
authors: TG
authors: Nunes
authors: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: Hermínio P
authors: HP
authors: Diogo
authors: IQUIR-CONICET, Suipacha 531, 2000 Rosario, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina. Electronic address: csalomon@fbioyf.unr.edu.ar.
authors: Claudio J
authors: CJ
authors: Salomon
authors: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal. Electronic address: m.joao.ferreira@tecnico.ulisboa.pt.
authors: M João
authors: MJ
authors: Ferreira
mesh_terms: D000871:Anthelmintics / Q000737:chemistry* / Q000378:metabolism; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization; D004339:Drug Compounding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011205:Povidone / Q000737:chemistry* / Q000378:metabolism; D011223:Praziquantel / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D012997:Solvents; D011223:Praziquantel; D011205:Povidone
keywords: DSC; Pharmaceutical formulations; Poly(vinylpyrrolidone); Praziquantel; Praziquantel (PubChem CID: 4891); Solid-state NMR