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Mller, M. ; Keler, B.
Release of pamidronate from poly(ethyleneimine)/cellulose sulphate complex nanoparticle films: An in-situ-ATR-FTIR study

In situ ATR-FTIR spectroscopy was used as a screening method to quantify the relative release of pamidronate (PAM) from films of polyelectrolyte (PEL) complex (PEC) particles. Stable colloid PEC particles consisting of poly(ethyleneimine) (PEI) and cellulose sulphate (CS) loaded with PAM were obtained by PEL complexation featuring hydrodynamic radii between 60 and 90nm and a cationic or anionic surface charge dependent on the mixing ratio n-/n+=0.9 or 1.1, respectively. Respective bare unloaded PEC particles showed smaller hydrodynamic radii. PAM loaded PEC particles were casted from dispersion onto Ge model substrates and dried forming stable films in contact to water. By in situ ATR-FTIR spectroscopy it could be shown, that PAM/PEC particle films contacting to water resulted in a time dependent retarded release of PAM from the PEC matrix, while PAM from a pure drug film was immediately released. Cationic PAM loaded PEC particles of PEI/CS showed smaller initial burst and long term release compared to anionic one at similar PAM/PEI ratios. With increasing PAM/PEI ratio the initial burst could be minimized to around 30% and the residual long term amount of PAM optimized to 50% for PAM/PEC samples casted from 0.002M dispersions. A further improvement of the release performance was achieved either by prerinsing the dry film in H2O or by rising the PEC concentration from 0.002M to 0.01M revealing an initial burst of around 5% and long term residual PAM content of around 75%. ATR-FTIR and TRANS-FTIR analysis of the PAM release from equivalent PEC samples revealed similar kinetic courses and parameters justifying the use of the Ritger/Peppas two parameter model. Applying this model PAM/PEC samples casted from 0.002M dispersions revealed exponent values of b0.5 suggesting PAM dissolution in the PEC matrix, while for those casted from 0.01M b values close to 0.5 were obtained suggesting hindered dissolution and diffusion. A model describing different retention modalities of PAM in PEC particle is suggested.

Journal of pharmaceutical and biomedical analysis : JPBA 66, 183-190


July 2012
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