Key words: screening methods, DoE, wet ball milling, nanosuspensions, granulation, dissolution
The Nanocrystal Technology by wet ball milling is getting more and more interest and importance for experts in formulation screening, tox study and clinical trial sample supply for low soluble API´s with a problem in bioavailability. The reason is a fast set-up and scale-up of the manufacturing process, the easy application of the liquid Nanocrystal formulations in such studies and the available down-processing possibilities to come to the final dosage form (capsules, tablets, stickpacks). Losan Pharma has invented in a cooperation a new and fast screening system for nano-milling which has meanwhile reached commercialisation (Zentrimix 380R® from Hettich Labs, Germany). In order to widen the application of the Nanocrystal system new surfactants with improved toxic and hemolytic properties in comparison to the reference sodium dodecyl sulfate (SDS) have been used with a model drug substance to evaluate their potential as stabilisers in the Nanocrystal suspensions. As SDS is very limited in use due to its toxicity especially for tox studies or parenteral applications new surfactants need to be developed to improve this situation. In addition a new down-processing approach is presented to embed the obtained Nanocrystal suspensions via a extrusion like process into a granulate (with the possibility of a continuous granulation) and a comparison has been made to the conventional fluid bed spray drying process which has been implemented before.