BCS-based biowaivers: Extension to paediatrics

Area of Science:

• Pharmaceutical Sciences
• Biopharmaceutics
• Paediatric Drug Development

Background:

• Biopharmaceutics Classification System (BCS)-based biowaivers simplify bioequivalence assessment for adult drug products.
• Paediatric populations may exhibit different drug solubility and permeability compared to adults.
• Extrapolation of adult BCS criteria to pediatric formulations requires careful consideration due to physiological differences.

Purpose of the Study:

• To identify compounds whose solubility classification may change between adult and pediatric populations.
• To assess the risks associated with applying BCS-based biowaiver criteria to pediatric drug products.
• To evaluate the suitability of current biowaiver conditions for pediatric formulation assessment.

Main Methods:

• Dissolution studies of amoxicillin, prednisolone, and amlodipine IR formulations were performed.
• USP II (paddle) and mini-paddle apparatus were used across three pH conditions (1.2, 4.5, 6.8).
• Three dissolution setups were tested: typical BCS biowaiver, adult bioequivalence (250 mL), and pediatric (50 mL) volumes.

Main Results:

• Drug solubility classification can differ between adult and pediatric populations.
• Scaling down volumes in dissolution testing does not automatically ensure the validity of BCS-based biowaivers for pediatric use.
• BCS-based biowaivers are not recommended when a drug's solubility class may change from adult to pediatric populations.

Conclusions:

• Extending BCS-based biowaivers to pediatric formulations is complex and not a simple volume adjustment.
• The risk of altered drug solubility in pediatric populations necessitates a cautious approach to BCS biowaiver application.
• Further research into the pediatric gastrointestinal environment is crucial for developing appropriate biopharmaceutical tools for pediatric drug formulation evaluation.