Excipient variability critically impacts crystallization propensity of spray-dried amorphous solid dispersions

Area of Science:

• Pharmaceutics
• Materials Science
• Chemical Engineering

Background:

• Polymeric amorphous solid dispersions (ASDs) enhance oral bioavailability of poorly water-soluble drugs.
• Stabilizer variability from different sources/batches can affect ASD stability and performance.
• Understanding these variations is crucial for consistent drug product manufacturing.

Purpose of the Study:

• To correlate physicochemical property variations of polymeric stabilizers with the stability of spray-dried ASDs.
• To identify key functionality-related characteristics (FRCs) and tests (FRTs) for stabilizer quality control.
• To ensure robust performance of spray-dried ASDs across different stabilizer batches and sources.

Main Methods:

• Spray drying of Polyvinylpyrrolidone-vinyl acetate (PVPVA) and griseofulvin (GSV) to form ASDs.
• Characterization of ASD amorphous state and homogeneity using pXRD, DSC, and PLM.
• Quantification of PVPVA functionality (% crystallization) and intermediate functionality (enthalpy relaxation) via pXRD and DSC.
• Measurement of various PVPVA physicochemical properties (Tg, viscosity, K-value, etc.).
• Correlation analysis (Pearson's) between PVPVA properties and ASD functionality.

Main Results:

• Amorphous and phase-homogeneous ASDs were confirmed.
• Strong correlations (r ≥ 0.6) found between ASD functionality and solvent evaporation kinetics, drug diffusion coefficient, K-value, and water activity increase.
• These correlations indicate significant drug-polymer and polymer-water interactions influencing ASD stability.

Conclusions:

• Functionality-related characteristics (FRCs) of polymeric stabilizers significantly impact spray-dried ASD stability.
• Proposed FRCs and FRTs can guide stabilizer selection and quality control for consistent ASD performance.
• This study provides a framework for ensuring robust ASD manufacturing for poorly soluble drugs.