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

The present study was conducted in order to probe the microstructure, micro viscosity, and hydration properties of matrices containing two model drugs, naproxen sodium (NS) and naproxen (N), and egg albumin (EA) as matrix carr ier. The results suggested that N release from EA matrix was controlled by a bulk erosion mechanism in combination with additional processes (crystal dissolution/ crystallization rate) compared with NS matrix, which behaved a s a non-erodible matrix and drug release occurred by diffusion through the gel. Using EPR technique it has been shown that incorporating NS into EA ma trix strongly influences the microstructure of the protein gel, and hence t he transport of the penetrant within the matrix, compared with matrices con taining N. The presence of NS increased the protein chain mobility and hydr ation which supports our previous results showing that NS cause unfolding o f EA. In contrast, N caused only marginal effect on EA chain mobility. The gel formed in EA/NS matrices was more porous compared with EA/N matrices as revealed by the lower rotational correlation time of PCA (lower microvisco sity) in EA/NS matrices compared with EA/N. However, EA/N gelled matrices w ere more heterogeneous, i.e., containing a higher number of components havi ng different mobility. The T-1 and T-2 relaxation studies by NMR provided a n additional support for the higher chain hydration in EA/NS matrices compa red with EA/N as indicated by the higher relaxation rates in the gelled mat rices. Internal pH measurements by EPR revealed that the micro-pH inside 10 0% EA and 50/50 EA/N matrices were lower than 50/50 EA/NS matrices and in a ll cases lower than the penetrating buffer pH. The lower pH compartment for med in N matrices affected N solubility and crystal dissolution rate, which can explain its lower release rate compared with EA, from the same formula tion. The EPR and NMR data supports our findings that NS caused unfolding o f the protein, affected matrix structure, and converted it to a hydrophobic non-erodible matrix compared with EA/N matrix in which the native properti es of EA were mainly retained. (C) 2000 Wiley-Liss, Inc. and the American P harmaceutical Association J Pharm Sci 89: 365-381, 2000.