Correlation between drug release kinetics from proteineous matrices and protein folding: elasticity and compressibility study

Naproxen sodium (NS) release mechanism from proteineous matrices based on e gg albumin (EA) and bovine serum albumin (BSA) was investigated by several physico-chemical methods. The gel strength, modulus of elasticity and erosi on properties of the matrices were studied and correlated with drug release kinetics. The results revealed that NS release rate from EA and BSA matric es was markedly different, indicating the significant role of protein natur e and conformation on matrix behavior. Unexpectedly it was found that incor poration of NS to EA matrix increased gel strength and modulus of elasticit y and decreased matrix erosion. This effect was dependent on NS concentrati on in the matrix. In contrast to EA, BSA behaved as a non-gelling matrix an d was unable to retard drug release because of its high solubility. The inf luence of NS on protein folding and compressibility in protein solutions wa s studied using densitometric and ultrasonic techniques. Adiabatic compress ibility measurements revealed that NS caused unfolding of EA, an effect whi ch led to a decrease in EA intrinsic compressibility and the exposure of at omic side groups buried in protein interior. Unfolding of EA led to an incr ease of modulus of elasticity in solution (measured by ultrasonic velocimet ry technique) which is in correlation with the modulus of elasticity measur ements of gelled tablets (measured by Instron). In concentrated EA solution s, the results showed a large increase in EA compressibility and ultrasonic absorption in the presence of NS indicating a strong aggregation of the de natured state of EA. Regarding BSA, the results suggested that NS affected the packing of the protein interior, transforming it to a molten globule in termediate state, an effect that led to an increase in BSA compressibility. At high BSA concentrations, aggregation of the molten globule state was ob served as indicated by an increase of BSA compressibility and ultrasonic ab sorption values. (C) 2000 Elsevier Science BN. All rights reserved.