In vitro analysis of the release of incorporated agents from sodium caseinate microspheres

Drug loaded microspheres were successfully prepared using the dairy protein, sodium caseinate (SC), as the carrier material and containing hydrochlorothiazide, eosin, patent blue violet and sodium salicylate. The morphology of the microspheres varied depending on the incorporated material. Release of the incorporated agents from these systems was rapid with over 90% release in each case within 1 h. Further drug release occurred at a greatly reduced rate with a certain proportion of the drug loading appearing to be indefinitely entrapped within some of the microspheres. The drug release profiles were poorly described using the square root of time and Sinclair and Peppas equations but were well described by a biexponential equation. Analysis of the parameter estimates from the biexponential equation indicated that the initial rapid release phase was essentially completed within 5 min for all but the eosin microsphere systems and this timeframe was of the same order of magnitude as that found for the initial swelling of these microsphere systems as analysed by swelling studies using optical microscopy. Considering both the swelling study and the results from the release experiments, it seems likely that addition of SC microspheres to aqueous media results in immediate hydration and swelling. This process facilitates the rapid diffusional passage of water soluble drugs through the swollen and hydrated microsphere matrix, with drug release occurring almost unhindered unless other factors favour the retention of the incorporated agent with the microsphere.