Dissolution studies of poorly soluble drug nanosuspensions in non-sink conditions.

Sink conditions used in dissolution tests lead to rapid dissolution rates for nanosuspensions, causing difficulties in discriminating dissolution profiles between different formulations. Here, non-sink conditions were studied for the dissolution testing of poorly water-soluble drug nanosuspensions. A mathematical model for polydispersed particles was established to clarify dissolution mechanisms. The dissolution of nanosuspensions with either a monomodal or bimodal size distribution was simulated. In the experimental part, three different particle sizes of indomethacin nanosuspensions were prepared by the wet milling technique. The effects of the dissolution medium pH and agitation speed on dissolution rate were investigated. The dissolution profiles in sink and non-sink conditions were obtained by changing the ratio of sample amount to the saturation solubility. The results of the simulations and experiments indicated that when the sample amount was increased to the saturation solubility of drug, the slowest dissolution rate and the best discriminating dissolution profiles were obtained. Using sink conditions or too high amount of the sample will increase the dissolution rate and weaken the discrimination between dissolution profiles. Furthermore, the low solubility by choosing a proper pH of the dissolution medium was helpful in getting discriminating dissolution profiles, whereas the agitation speed appeared to have little influence on the dissolution profiles. This discriminatory method is simple to perform and can be potentially used in any nanoproduct development and quality control studies.