Milling and comilling Praziquantel at cryogenic and room temperatures: Assessment of the process-induced effects on drug properties

Zanolla, Debora; Perissutti, Beatrice; Passerini, Nadia; Invernizzi, Sergio; Voinovich, Dario; Bertoni, Serena; Melegari, Cecilia; Millotti, Gioconda; Albertini, Beatrice

doi:10.1016/j.jpba.2018.02.018

Cited by 29 publications

(26 citation statements)

References 33 publications

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“…HPLC results showed a complete drug recovery after mechanical treatment, attesting the lack of chemical changes in PZQ. This means that when PZQ is ground in the presence of little amounts of water (equimolar) does not degrade, similarly to what was noted when grinding PZQ alone [19,20], but unlike what was seen in the presence of polymeric excipients [22][23][24]. This also highlights that the presence of water, at least in little amounts during milling does not favor chemical degradation, even though water is known to be a factor affecting PZQ chemical stability [22].…”

Section: Chemical Analysesmentioning

confidence: 69%

“…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]. Such solid dispersions, however, presented a diminished drug recovery, which was found to be dependent on the polymer used [23,24]. Conversely, when PZQ is processed alone by neat grinding maintains a conspicuous residual crystallinity and does not degrade [19,20].…”

Section: Introductionmentioning

confidence: 99%

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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: Chemical Analysesmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

et al. 2020

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“…HPLC analysis was also used to calculate the solubility and the dissolution properties of the different samples. The method was adapted from literature [26] and have been already validated and employed for PZQ quantification in previous studies [11,12,13]. Briefly, the HPLC system consisted of two mobile phase delivery pumps (LC-10ADvp, Shimadzu, Japan) and a UV–vis detector (SPD-10Avp, Shimadzu, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…From the biopharmaceutical point of view, several approaches have been undertaken to reduce the PZQ therapeutic dose, due to its solubility enhancement [7,9,10]. Recently we have proposed some strategies involving the mechanochemical activation of the drug, proving the amelioration of the PZQ biopharmaceutical properties (solubility, intrinsic dissolution rate (IDR)) [11,12,13]. In particular, in the first study, PZQ was coground with different pharmaceutical polymers, using a lab-scale vibrational mill and an explorative analysis of formulation variables (drug-polymer wt.…”

Section: Introductionmentioning

confidence: 99%

“…From both experiences it was clear that the drug, when comilled in presence of polymers, was more prone to amorphization and a certain amount of degradation. Conversely, PZQ that was ground by itself, did not show this propensity to degradation while maintaining the tendency to physical transformations [13]. In addition, when subjected to neat grinding in adequate conditions, PZQ evidenced to form an anhydrous polymorphic variety with a very high efficiency.…”

Section: Introductionmentioning

confidence: 99%

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Combining Mechanochemistry and Spray Congealing for New Praziquantel Pediatric Formulations in Schistosomiasis Treatment

Albertini

Perissutti

Bertoni

et al. 2019

IJMS

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Praziquantel (PZQ) is the first line drug for the treatment of schistosome infections and is included in the WHO Model List of Essential Medicines for Children. In this study, the association of mechanochemical activation (MA) and the spray congealing (SC) technology was evaluated for developing a child-friendly PZQ dosage form, with better product handling and biopharmaceutical properties, compared to MA materials. A 1:1 by wt PZQ—Povidone coground—was prepared in a vibrational mill under cryogenic conditions, for favoring amorphization. PZQ was neat ground to obtain its polymorphic form (Form B), which has an improved solubility and bioactivity. Then, activated PZQ powders were loaded into microparticles (MPs) by the SC technology, using the self-emulsifying agent Gelucire® 50/13 as a carrier. Both, the activated powders and the corresponding loaded MPs were characterized for morphology, wettability, solubility, dissolution behavior, drug content, and drug solid state (Hot Stage Microscopy (HSM), Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction Studies (PXRD), and FT-IR). Samples were also in vitro tested for a comparison with PZQ against Schistosoma mansoni newly transformed schistosomula (NTS) and adults. MPs containing both MA systems showed a further increase of biopharmaceutical properties, compared to the milled powders, while maintaining PZQ bioactivity. MPs containing PZQ Form B represented the most promising product for designing a new PZQ formulation.

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Preferential Oxycodone Loss of Physically Manipulated Abuse Deterrent Oxycodone HCl Extended Release Tablets Prepared for Nasal Insufflation Studies

et al. 2021

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Milling and comilling Praziquantel at cryogenic and room temperatures: Assessment of the process-induced effects on drug properties

Cited by 29 publications

References 33 publications

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Combining Mechanochemistry and Spray Congealing for New Praziquantel Pediatric Formulations in Schistosomiasis Treatment

Preferential Oxycodone Loss of Physically Manipulated Abuse Deterrent Oxycodone HCl Extended Release Tablets Prepared for Nasal Insufflation Studies

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