Susanne MUSCHERT

University of Lille, France

Title: Drug release mechanisms from coated pellets : How non-invasive analytical tools can help to comprehend them

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Biography

Abstract

Drug release mechanisms from coated sustained release pellets can be very complex. However, they need to be fully understood in order to guarantee the safety of a pharmaceutical treatment.

Pellets coated with Kollicoat SR:Kollicoat IR 95:5 and 90:10 blends and loaded with verapamil HCl have been in the center of this study. Drug release fromthese coated pellets is highly dependent on the pH of the dissolution medium. To better understand the underlying drug release mechanisms, next to ensemble of pellets also single pellets have been analyzed. Raman spectroscopy and SEM were used to determine if crack or pore formation play a major role. An application of a mathematical modeling using a mechanistically realistic theory to describe drug release kinetics with this particular reservoir system, revealed that diffusion is rather unlikely to play a major role in mass transport mechanisms. The pH inside the pellets detected by means of pH sensitive fluorescence probes differed significantly upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4. Since verapamil is a weak base, drug solubility decreased at higher pH, this led to lower drug release rates in basic media from coated single pellets as well as an ensemble of pellets. The swelling of single pellets, observed with optical light microscopy, indicated that crack formation in the polymeric film occurs. SEM and Raman imaging further confirmed this fact. Raman spectroscopy also permitted to observe changes in the coating and close core layers of the pellets non-invasively during dissolution.