Study of Rheology and Polymer Adsorption Onto Drug Nanoparticles in Pharmaceutical Suspensions Produced by Nanomilling.

Nanosuspensions provide a drug delivery approach to cope with erratic absorption of poorly water-soluble compounds. Despite extensive research over the last years, there are still open pharmaceutical challenges so it is often unclear how quality attributes such as viscosity and physical stability are generated, which requires a more thorough study of the colloidal structures and interactions in nanosuspensions. In this study, diffusing wave spectroscopy and microfluidics-based rheology were used for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Further sample characterization following centrifugation was based on optical rotatory dispersion and conductivity experiments. Ketoconazole was selected as model drug in the presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively. The results unexpectedly showed that the investigated nanosuspensions did not behave as Einstein-like suspensions because a viscosity decrease was evidenced for increased drug load. This effect was attributed to the polymer that formed a dominating network in the bulk solution from where adsorption occurred onto particle surfaces. This depletion of bulk polymer caused the observed rheological finding. Further colloidal research should be invested into different pharmaceutical nanosuspensions to gain a more complete structural understanding and to harness their full technological potential.