Dissocaubes Case Study

DissoCubes®,
I. INTRODUCTION About 10% of the drugs developed by now are poorly soluble and have bioavailability problems. Estimations for the future envisage that about 40% of the newly developed drugs will be poorly soluble and as a result will show problems for attaining a therapeutically significant blood level. Thus, there is a crucial demand to find solutions for the fabrication of these poorly soluble drugs. Preferably, such a new formulation principle should be relevant to almost any poorly soluble drug independent of its chemical structure and spatial molecular dimensions. A simple methodology to enhance the bioavailability of orally administered drugs is micronization. However the drugs with low saturation solubility might not lead
Thus, alternate formulation techniques to prevailing approaches [1,2] need to be discovered. To acquire a broadly relevant technology, keen interest has been focused on drug nanoparticles in the last few years. Going beyond micronization bring about a further increase in the dissolution velocity due to an even larger surface area. Examples of this are the so-called Hydrosols developed by Sucker [3–6] and NanoCrystals offered by NanoSystems, a division of Elan Pharmaceutical Technologies [7–9]. An extra effect can be acquired by a controlled structural change in drug nanoparticles, which means decreasing the crystallinity and increasing the amorphous fraction. Examples of drug nonoparticles with structural changes are the products NanoMorph marketed by Knoll/BASF Pharma (company brochure) and the drug nanosuspensions marketed under the name DissoCubes [10,11]. DissoCubes bring together the benefits of using a size reduction technique (i.e., NonoCrystals) with the advantages of a precipitation technique (i.e., Hydrosols, NanoMorph) opening the opportunity to cause structural changes which means increasing
The increase in dissolution velocity is because of increase in surface area going beyond that of micronized products. Fine powders/particles retain an increased adhesiveness very well known from powder technology. These features enhance bioavailability. Much in vivo data generated with drug nanoparticles by NanoSystems confirm this [22]. However, there are two more remarkable features of drug nanoparticles (i.e., DissoCubes): (a) an increase in saturation solubility and (b) structural changes inside the particles. The latter depends very much on the means of production (e.g., introduction of high energy to increase the amorphous fraction as performed by high-pressure