A Risk-Based Framework for Hospital Compounding: Integrating Degradation Mechanisms and Predictive Toxicology

Area of Science:

• Pharmaceutical Sciences
• Drug Formulation
• Predictive Toxicology

Background:

• Hospital compounding is crucial for personalized therapies, especially in pediatrics and oncology.
• Growing demand and new regulations (e.g., UK MHRA Guidance) increase the need for robust compounding practices.
• Drug degradation during compounding poses risks to stability, impurity control, and reproducibility.

Purpose of the Study:

• To develop a risk-based scientific framework for hospital drug formulation.
• To integrate drug degradation profiling with predictive toxicology for safer compounding.
• To provide structured guidance for formulation strategies in the absence of pharmacopeial monographs.

Main Methods:

• Forced-degradation studies (hydrolytic, oxidative, photolytic) and ab initio modeling to identify degradation pathways.
• A structured decision tree for formulation strategies (solvent, pH, excipients, packaging).
• In silico toxicological assessment of degradation products aligned with ICH M7 guidelines to define CQAs and CPPs.

Main Results:

• Demonstrated framework applicability through hospital compounding case studies.
• Extended the framework for advanced applications like semi-solid extrusion (SSE) 3D printing.
• Successfully integrated mechanistic understanding of drug degradation into formulation planning.

Conclusions:

• The proposed framework enhances safety, reproducibility, and quality of compounded preparations.
• Reinforces Good Preparation Practices (GPPs) and aligns with Quality-by-Design (QbD) principles.
• Supports the development of personalized medicine through improved compounding strategies.