Lessons Learned from Pharmaceutical Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 121

property needs to be evaluated for their tunability. Currently, we manage to tune size
and/or shape by the use of special methods. As a goal our particle manufacturing
methods need to be able to control all crucial properties at the same time.
Following as far as possible and reasonable QbD attempts will lead to the creation
of high quality results in research. The sharing of these results in publications and
databases with open access will help to organize and sort the gained knowledge.
Academic partners alone cannot do this—large cooperation projects best with indus-
trial partners or public funded institution would be needed for such work. Statistical
analysis, modeling, and prediction (e.g., NanoQSAR [Puzyn et al. 2011]) would be
of high benefit in such interdisciplinary and wide scientific area. The development of
high throughput analytical methods to manage the large number of needed tests for
process validation is a further need in nanomaterial science.
From the plurality of developed drug carriers in the controlled environment of in
vitro experiments many smart drug delivery systems perform well. Maintenance of
the performance in the environment of complex biological systems (i.e., in vivo) is
another category of challenge. The systems which already managed the translation
into the clinics are often systems which not only take account of the physiology but
also sometimes even draw advantages of it as, for example, Abraxane ® gaining from
the binding of albumin.
6.5 NANOPHARMACEUTICALS STATE OF THE ART
Contemplating today's pharmaceutical industry, nanoparticulate systems showed
importance on the market over the last few decades and promise rising potential
for the future. Birrenbach and Speiser (1977) started to synthesize “nanoparts” for
pharmaceutical application as early as in 1976. They distinguished between nano-
capsules, such as shell-like polymer constructions, and nanopellets also known as
compact polymer particles. Materials and techniques used at that time proved to be
problematic in terms of toxicity. As a consequence, preparation methods and mate-
rials had to be substituted, further optimized, or newly developed. From nineties
onwards, various nanoparticulate formulations for pharmaceutical applications have
been approved by the FDA and are currently on the market.
6.5.1 a PPliCation f ields : W hy to u se n anoPharmaCeutiCals
One reason to design nanoparticulates for pharmaceutical applications is their
potential to successfully reformulate traditional formulations to overcome articula-
tion problems, due to poor water solubility of the drug (Bawa 2008). An example
for optimizing the performance of APIs is the Nanocrystal ® technology: Reducing
the size of particles to the nano range via wet-milling and subsequent stabilization
of the drug particles results in a stable product with substantially increased sur-
face area, improved water solubility, and hence bioavailability (Merisko-Liversidge,
Liversidge, and Cooper 2003; Liversidge 1992; Liversidge and Cundy 1995).
Sirolimus (Rapamune ® ), approved by the FDA in 1999, is the first marketed drug,
developed with this technology. Fenofibrate (TriCor ® ) and Aprepitant (Emend ® )
are other examples of reformulated FDA-approved therapeutics, which employ this