From Bitter to Sweet: a preliminary study towards a patient-friendly Praziquantel dosage form

Praziquantel (PZQ) is an antihelmintic drug used worldwide against Schistosomiasis, despite its low solubility, bioavailability and the disgusting taste. This research represents a preliminary screening of 6 selected sweeteners in terms of their aptitude to be ground with PZQ, towards the development of a patient-friendly dosage form, capable of overcoming both dissolution and taste drawbacks. A vibrational mill was used to process equimolar mixtures of PZQ and each sweetener, and the dispersions were characterized by means of Differential Scanning Calorimetry, Powder X-ray Diffraction, Fourier Transform-Infrared Spectrometry, water solubility and Intrinsic Dissolution Rate. Physical stability of the coground systems was checked over a period of 1 year. The grinding for a short period (such as 30 min) of PZQ and selected sweeteners led to several very interesting products, with prevalent amorphous character, enhanced solubility and Intrinsic Dissolution Rate comparing to the raw drug. Peculiar behavior was found in the case of xylitol:PZQ ground mixtures where the appearance of traces of PZQ anhydrous Form B was noticed. Therefore, this research highlights the possibility of using binary premixes of PZQ and sweeteners in order to obtain an increase in the biopharmaceutical and organoleptic properties of the anthelmintic drug, underlining also the need for a careful screening of sweetener to design a PZQ patient-friendly dosage form.

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Materials

Praziquantel (PZQ, (11bRS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4-H-(pyrazino[2,1-a]isoquinolin-4-one)) of Ph. Eur. grade was kindly donated by Fatro S.p.a. (Bologna, Italy). Mannitol (MAN), xylitol (XYL), maltitol (MAL), sorbitol (SOR), sucralose (SUC) and aspartame (ASP) were from Galeno S.r.l. (Carmignano, PO, Italy). The HiPersolv Chromanorm methanol used for the HPLC analysis was of Ph. Eur. grade and purchased from VWR Chemicals (BHD PROLABO^® Milano, Italy).

Debora Zanolla; Serena Bertoni; Nadia Passerini; Beatrice Albertini; Guglielmo Zingone; Beatrice Perissutti. From Bitter to Sweet: a preliminary study towards a patient-friendly Praziquantel dosage form. Comptes Rendus. Chimie, Volume 25 (2022), pp. 179-188. doi : 10.5802/crchim.188. https://comptes-rendus.academie-sciences.fr/chimie/articles/10.5802/crchim.188/

What are sweeteners? See our introduction article