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Marker-ion analysis for quantification of mucoadhesivity of microparticles in particle-retention assays.

International journal of pharmaceutics (2015-04-18)
Daniel Preisig, Michael Weingartner, Felipe J O Varum, Roberto Bravo, Rainer Alles, Jörg Huwyler, Maxim Puchkov
ABSTRACT

The objective of the present work was to develop an improved method to quantify particle retention on mucosal tissue under dynamic flow conditions with simultaneous determination of drug dissolution. The principle was to dissolve the collected inert carrier material and quantify specific marker ions by reliable analytical methods. The mucoadhesive model particles consisted of drug-loaded porous calcium carbonate microcarriers coated with chitosan, and quantification of calcium ions by capillary electrophoresis enabled to determine particle-retention kinetics on colonic mucosal tissue. The method was validated by image analysis, and the particle-retention assay was successfully applied to granulate material (125-250 mm) and small particles (<90 μm) with mucoadhesive properties. Particle retention on colonic mucosa was improved by increasing the chitosan content, demonstrating the sensitivity and usefulness of marker-ion analysis for quantification of detached particles. Furthermore, we showed that drug dissolution from mucoadhesive microparticles followed comparable kinetics in the particle-retention assay and the standard USP IV method. Our findings are helpful for the development of micro-sized colonic drug delivery systems, in particular for optimization of mucoadhesive properties and sustained drug release kinetics of porous drug carriers.

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