Preparation and characterization of a new solid form of praziquantel, an essential anthelmintic drug. Praziquantel racemic monohydrate

Salazar-Rojas, Duvernis; Maggio, Rubén M.; Kaufman, Teodoro S.

doi:10.1016/j.ejps.2020.105267

Cited by 18 publications

(21 citation statements)

References 37 publications

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“…Both PZQ Form B and Form C preserve the activity against Schistosoma and have an improved water solubility [19,20]. Very recently, other authors have proposed a further solid form, not indexed in the CSD, reported as a pink powder; however, the performed characterizations neither allowed to solve the structure nor to validate it [21]. Moreover, our group has also reported the possibility of obtaining PZQ in a highly amorphous state, physically stable for several months, by a mechanochemical treatment in the presence of different polymeric excipients [22].…”

Section: Introductionmentioning

confidence: 97%

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

et al. 2020

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Praziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been discovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of multicomponent forms of PZQ a relevant example of a racemic hemihydrate (PZQ-HH), obtainable from commercial PZQ (polymorphic Form A) through mechanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, polarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diffraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed peculiar biopharmaceutical features including enhanced solubility and a double intrinsic dissolution rate in water in comparison to the commercially available PZQ Form A.

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Section: Introductionmentioning

confidence: 97%

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

et al. 2020

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“…Zanolla et al recently reported two anhydrate polymorphic forms, i.e., form B (CSD refcode-TELCEU01) and form C (CSD refcode-GOYZOM), that are produced via neat grinding of the commercial form A of PRA for about 4 h in a vibrational mixer mill. A racemic hemihydrate form of PRA obtained through mechanochemistry is also depicted by this group and a monohydrate form by Salazar-Rojas et al…”

Section: Introductionmentioning

confidence: 79%

“…It is a chiral prescribed drug for the treatment of schistosomiasis worms . A background survey of PRA reveals that it has three reported polymorphs, several cocrystals, and also hydrates. − The marketed form A is a racemic compound with a triclinic crystal structure (CSD refcode-TELCEU) . It has a disordered structure with two out of four molecules that are disordered in the asymmetric unit, the carbonyl groups have syn conformation .…”

Section: Introductionmentioning

confidence: 99%

“…22 Zanolla et al recently reported two anhydrate polymorphic forms, i.e., form B (CSD refcode-TELCEU01) 18 and form C (CSD refcode-GOYZOM), 23 that are produced via neat grinding of the commercial form A of PRA for about 4 h in a vibrational mixer mill. A racemic hemihydrate form 17 PRA obtained through mechanochemistry is also depicted by this group and a monohydrate form by Salazar-Rojas et al 20 In this study, we are particularly interested in the role of mechanochemistry in solid form selection and identification of PRA, particularly investigating the polymorphism of PRA by using the VALAG technique. We identified and investigated a new polymorphic anhydrous crystalline form of PRA (designated as form D) from neat grinding.…”

Section: Introductionmentioning

confidence: 99%

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Role of Mechanochemistry in Solid Form Selection and Identification of the Drug Praziquantel

Saikia

Seidel‐Morgenstern

Lorenz

2021

Crystal Growth & Design

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Identification of all possible polymorphs for a pharmaceutical compound is vital for the better formulation of medicine with desired properties. This study demonstrates the application of a mechanochemical approach to reveal new polymorphs of a drug and the potential of variable amounts of solvent in liquid-assisted grinding for solid form screening. Without solvent and by varying the amount of solvent added, we found two new polymorphs and an amorphous form, which were not reported previously. The finding portrays the advantage of the mechanochemical approach as a means of the polymorph screening strategy. While the focus here was on praziquantel, a similar approach is applicable to other pharmaceutical systems. This study also contributed to reinvestigate the solid-state behavior of the chiral praziquantel system, including the melt phase diagram and the role of experimental conditions on its phase behavior.

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“…Praziquantel 28 (PZQ; Figure 1) is an anthelmintic drug used in the preventive treatment against schistosomiasis, a disease caused by parasitic flatworms, and suffers from a number of the abovementioned issues. Due to its poor solubility in aqueous media, the drug is classified as a BCS class II drug i , and efforts to improve its solubility and dissolution profile by screening for polymorphs, [29][30][31][32][33][34] hydrates, 35 and co-crystals 29,36,37 have previously been reported. Additionally, while PZQ is currently administered as a racemate, the R-enantiomer possesses the desired therapeutic activity, [38][39][40][41] and the S -enantiomer, the distomer, is held i The Biopharmaceutics Classification System classifies drugs into four categories based on their solubility and permeability.…”

Section: Introductionmentioning

confidence: 99%

Co-crystals of Praziquantel: Discovery by Network-Based Link Prediction

Devogelaer¹,

Charpentier²,

Tijink³

et al. 2021

Preprint

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Preparation and characterization of a new solid form of praziquantel, an essential anthelmintic drug. Praziquantel racemic monohydrate

Cited by 18 publications

References 37 publications

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Role of Mechanochemistry in Solid Form Selection and Identification of the Drug Praziquantel

Co-crystals of Praziquantel: Discovery by Network-Based Link Prediction

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