Preformulation and Long-Term Stability Studies of an Optimized Palatable Praziquantel Ethanol-Free Solution for
Giselle Bedogni1, Paula Garcia2, Katia Seremeta3
1Instituto de Química Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas (IQUIR-CONICET), Suipacha 531, Rosario 2000, Argentina.
Insights
This study developed a palatable oral praziquantel solution for treating cysticercosis, overcoming challenges in pediatric drug formulation. The new solution significantly enhances praziquantel solubility and masks bitterness, offering a viable alternative for widespread treatment.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Infectious Diseases
Background:
- Cysticercosis and neurocysticercosis treatments rely on praziquantel, typically administered orally as tablets.
- The tablet form of praziquantel presents administration challenges, especially for pediatric patients.
- Praziquantel's poor water solubility complicates the development of liquid formulations.
Purpose of the Study:
- To develop a palatable, stable oral solution of praziquantel.
- To enhance praziquantel solubility for improved pediatric administration.
- To mask the bitter taste of praziquantel in a liquid formulation.
Main Methods:
- Utilized a design of experiments approach to optimize co-solvent systems for praziquantel solubility.
- Incorporated pharmaceutical-accepted co-solvents and taste-masking agents (flavors, sweetener).
- Conducted taste masking assays with human volunteers and stability studies at various temperatures (4°C, 25°C, 40°C) for 12 months.
Main Results:
- Achieved a significant increase in praziquantel solubility, from 0.38 mg/mL to 43.50 mg/mL in the optimized co-solvent system.
- Successfully reduced the bitterness of praziquantel through the addition of flavors and a sweetener, confirmed by human volunteers.
- Praziquantel impurities remained within United States Pharmacopeia (USP) acceptance criteria during 12-month stability studies.
Conclusions:
- Developed a novel, palatable, and stable oral praziquantel solution suitable for pediatric use.
- The optimized co-solvent system significantly enhances praziquantel solubility, addressing a key formulation challenge.
- This formulation represents a promising alternative for preclinical studies and widespread treatment of cysticercosis and neurocysticercosis.
Abstract:
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.
