Solution calorimetry as an alternative approach for dissolution testing of nanosuspensions.

The formulation of poorly soluble drugs as nanocrystals/nanosuspensions has rapidly evolved during the past decade into a mature drug-delivery strategy. The major characteristic of these systems is the high drug dissolution rate, enabling bioavailability enhancement after oral administration. It is therefore of great importance to have access to analytical methodology that is able to accurately monitor the extreme fast dissolution process of such formulations. The aim of the present study was to evaluate solution calorimetry as a novel approach to measure the dissolution rate of nanosuspensions by recording the temperature change in the dissolution vessel during the dissolution process of the nanocrystals. The applicability was tested on different nanosuspensions made up of three model drugs: naproxen, cinnarizine and an investigational API, i.e. compound A. The dissolution process of all nanosuspensions investigated was completed within less than 1 min. During this period, sufficient data points were collected to transform temperature offset data to cumulative heat of solution pointing to the potential of this technique. However, of significant concern is the fact that this technique measures the total heat produced or consumed by all processes that occur during the dissolution, e.g. the heat of mixing when the nanosuspension comes in contact with the dissolution medium. Erroneous conclusions will result if phenomena other than dissolution are not accounted for.