Sneha V Sawant et al., IJSID 2011, 1 (3), 1-15
International Journal of Science Innovations and Discoveries, Volume 1, Issue 3, November-Deceber 2011
It is estimated that 40% or more of active substances being identified through combinatorial screeningprograms are poorly soluble in water. Poor solubility is not only a problem for the formulation development andclinical testing; it is also an obstacle at the very beginning when screening new compounds for pharmacologicalactivity. From this, there is a definite need for smart technological formulation approaches to make such poorlysoluble drugs bioavailable. Making such drugs bioavailable means that they show sufficiently high absorption afteroral administration, or they can alternatively be injected intravenously.
Since many years the approaches toincrease drug solubility are solubilisation by surfactants, complex formation (e. g. cyclodextrin, macromolecules)self-emulsifying drug delivery systems (SEDDS), microemulsions and especially for oral administrationmicronisation of drug powders
. Micronization, meaning the transfer of drug powders into the size rangebetween typically 1-10μm. However, nowadays many drugs are so poorly soluble that micronization is not sufficient. The increase in surface area, and thus consequently in dissolution velocity, is not sufficient to overcomethe bioavailability problems of very poorly soluble drugs of the biopharmaceutical specification class II. Aconsequent next step was to move from micronization to nanonization. At the beginning of the 1990s the drugnanocrystals were developed as more efficient approach to increase drug solubility and dissolution velocity.Instead of micronising the drug powder, it is nanonised leading to nanocrystals with a typical size of about 200 nmup to approximately 600 nm. Drug nanocrystals can be used for a chemical stabilization of chemically labile drugs.The drug paclitaxel can be preserved from degradation when it is formulated as a nanosuspension.
The sameresult was found for the chemically labile drug omeprazole when formulated as a nanosuspension, the stability wasdistinctly increased in comparison to the aqueous solution.
Increasing Dissolution through Nanonization
Most differentiating features of drug nanocrystals are the increased saturation solubility and theaccelerated dissolution velocity. A drug specific constant which depends only on the solvent and the temperature iscalled as the saturation solubility (Cs). As described by the Nernst Brunner/Noyes-Whitney equation
, the solidAPI dissolution rate is proportional to the surface area available for dissolution as discussed belowWhere, dx/dt= dissolution rate, Xd = amount dissolved, A= particle surface area, D = dissolution rate constant,V = volume of fluid available for dissolution, Cs =saturation solubility, h = effective boundary layerthickness.Hence, due to further decrease in the particle size in the sub-micron range will further increase dissolutionrate because of increase insurface area. Furthermore, as explained by the Prandtl equation, the diffusion layerthickness will also be reduced, thus resulting in an enhanced dissolution rate.
An increase in saturation solubilityof the nanosized API has also been explained by the Freundlich–Ostwald equation: