Preformulation and Long-Term Stability Studies of an Optimized Palatable Praziquantel Ethanol-Free Solution for Pediatric Delivery

To date, the treatment for cysticercosis and neurocysticercosis consists of a single oral intake of praziquantel (5–10 mg/kg), which since it is only available as tablets, hinders its administration to pediatric patients. Praziquantel is a poorly water-soluble drug which represents a challenge for its formulation in solution, particularly for the pediatric population. Thus, this study aimed to develop a palatable solution for praziquantel using pharmaceutical-accepted co-solvent systems. A design of experiments approach was applied to identify the optimal conditions for achieving a suitable amount of praziquantel in solution using co-solvent mixtures. Thus, praziquantel solubility increased from 0.38 up to 43.50 mg/mL in the optimized system. A taste masking assay in healthy human volunteers confirmed a successful reduction of drug bitterness after the addition of selected flavors and a sweetener. Stability studies were also conducted at different temperatures (4, 25, and 40 °C) for 12 months Even though the presence of the three known impurities of praziquantel was observed, their amounts never exceeded the acceptance criteria of the USP. Thus, this novel approach should be considered a valuable alternative for further preclinical studies considering the high prevalence of this infection worldwide.

2.1. Materials

PZQ (lot PE13604) was purchased from Unifarma (Buenos Aires, Argentina). PEG 400 (lot 14042017) and PPG (lot 14442016) were purchased from Biopack (Buenos Aires, Argentina). NMP (Pharmasolve™, lot 05600168383) was purchased from Ashland (Texas City, TX, USA). Sodium dihydrogen phosphate (Biopack, lot 11585, 99.60% purity), sodium hydrogen phosphate (Biopack, lot 21100, 99.60% purity), methylparaben sodium salt (Novalquim SRL lot 23585, 99.55% purity), mint flavor (Parafarm, lot 49134, 99.30% purity), strawberry flavor (Parafarm, lot 45616, 99.40% purity), and sucralose (Parafarm, lot 41349, 99.55% purity) were purchased from Saporiti (Buenos Aires, Argentina). Water used herein was ultrapure MilliQ water filtered through a pore size of 0.22 μm. United State Pharmacopeia (USP) standards: USP Praziquantel RS, USP Praziquantel Related Compound A RS (2-benzoyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino [2,1-a]isoquinolin-4-one), USP Praziquantel Related Compound B RS (2-(cyclohexyl carbonyl)-2,3,6,7-tetrahydro-4H-pyrazino [2,1-a]isoquinolin-4-one) and USP Praziquantel Related Compound C RS (2-(N-formylhexahydrohippuroyl)-1,2,3,4-tetrahydroisoquinolin-1-one) was obtained from the United States Pharmacopeial Convention (Rockville, MD, USA). Acetonitrile HPLC-grade was supplied by J.T. Baker (Madrid, Spain). All the other reagents and solvents used in this study were of analytical grade.

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Bedogni, G.; Garcia, P.; Seremeta, K.; Okulik, N.; Salomon, C. Preformulation and Long-Term Stability Studies of an Optimized Palatable Praziquantel Ethanol-Free Solution for Pediatric Delivery. Pharmaceutics 2023, 15, 2050.
https://doi.org/10.3390/pharmaceutics15082050

excipients formulation