Nanoparticle PBPK model

Nanoparticle PBPK model simulates physiologically based pharmacokinetic behavior of nanoparticle formulations to evaluate and optimize systemic delivery of poorly soluble drugs such as SNX-2112.

Key Features:

• Physiologically Based Pharmacokinetic (PBPK) modeling: Implements PBPK modeling to simulate drug disposition in biological systems, including rats.
• SimBiology integration: Integrates SimBiology modeling capabilities for constructing and simulating mechanistic PBPK models.
• Concentration index and NCA: Performs concentration index (CI) calculations and non-compartmental analysis (NCA) for pharmacokinetic characterization.
• Parallel computing: Leverages parallel computing to accelerate simulations and analyses.
• Particulate uptake modeling: Includes parameters to model particulate uptake into organs such as the liver and spleen.
• In vivo release dynamics: Models in vivo release dynamics of drug from nanoparticles and predicts rapid release behavior observed with nanocrystals.
• Formulation scenario comparison: Supports simulation of administration scenarios including cosolvent and nanocrystal formulations for comparative pharmacokinetics.
• Experimental characterization integration: Incorporates experimental metrics such as particle size, differential scanning calorimetry, and drug release profiles.
• Formulation-specific properties: Represents formulation properties including wet-media milling preparation, poloxamer 188 stabilization, particle size of approximately 203 nm, and zeta potential of -11.6 mV for SNX-2112 nanocrystals.

Scientific Applications:

• Pharmacokinetic evaluation: Evaluates and optimizes pharmacokinetic profiles of nanoparticle-based drug formulations.
• Formulation development for poorly soluble drugs: Supports development and optimization of nanocrystal formulations for poorly soluble agents such as SNX-2112.
• Biodistribution analysis: Predicts biodistribution and particulate uptake in organs including the liver and spleen.
• Comparative formulation assessment: Compares pharmacokinetic behavior of nanocrystal formulations versus cosolvent formulations.
• In vivo release interpretation: Aids interpretation of in vivo drug release kinetics from nanoparticles and their impact on systemic exposure.

Methodology:

Uses SimBiology-based PBPK modeling with concentration index (CI) and non-compartmental analysis (NCA), leverages parallel computing, and includes model components for particulate uptake and in vivo release dynamics in rat simulations.