Correlation between drug release kinetics from proteineous matrix and matrix structure: EPR and NMR study

Area of Science:

• Materials Science
• Pharmaceutical Sciences
• Biophysics

Background:

• Drug delivery systems often utilize protein-based matrices for controlled release.
• Understanding the interaction between model drugs and protein carriers is crucial for formulation design.
• Egg albumin (EA) is a potential matrix carrier for drugs like naproxen (N) and its sodium salt (NS).

Purpose of the Study:

• To investigate the microstructure, microviscosity, and hydration of egg albumin (EA) matrices containing naproxen sodium (NS) and naproxen (N).
• To elucidate the drug release mechanisms of NS and N from EA matrices.
• To characterize the influence of NS and N on the structural and dynamic properties of the EA matrix.

Main Methods:

• Electron Paramagnetic Resonance (EPR) spectroscopy to probe microstructure, microviscosity, and internal pH.
• Nuclear Magnetic Resonance (NMR) relaxation studies (T(1) and T(2)) to assess hydration.
• Drug release studies to determine release kinetics.

Main Results:

• NS incorporation into EA matrices led to increased protein chain mobility, hydration, and porosity, resulting in a non-erodible matrix and diffusion-controlled NS release.
• N incorporation into EA matrices had a marginal effect on protein chain mobility, retaining EA's native properties and leading to a heterogeneous matrix with bulk erosion and dissolution-controlled N release.
• Internal pH measurements indicated lower micro-pH in EA/N matrices compared to EA/NS matrices, affecting N solubility and release rate.

Conclusions:

• NS transforms EA into a hydrophobic, non-erodible matrix, facilitating diffusion-driven release.
• N retains EA's native properties, leading to a more erodible matrix and dissolution-controlled release.
• The distinct interactions of NS and N with EA significantly alter matrix properties and drug release mechanisms.