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jensuwe a h junghanns introduction since the last ten years, the number of poorly soluble drugs is oxycodone ibuprofen steadily increasing according to estimates, about of the drugs in the pipelines have solubility problems the increased use of high throughput screening methods leads to the discovery of more drugs being poorly water soluble in the literature, figures oxycodone ibuprofen are quoted that about percent of the drugs coming directly from synthesis are nowadays poorly soluble poor solubility is not only a problem for the formulation development and clinical testing, it is also an obstacle at the very oxycodone ibuprofen beginning when screening new compounds for pharmacological activity from this, there is a definite need for smart technological formulation approaches to make such poorly soluble drugs bioavailable making such drugs bioavailable means that they show sufficiently high absorption oxycodone ibuprofen after oral administration, or they can alternatively be injected intravenously there is quite a number of formulation approaches for poorly soluble drugs which can be specified as specific approaches these approaches are suitable for molecules having special properties oxycodone ibuprofen with regard to their chemistry eg solubility in certain organic media or to the molecular size or conformation eg molecules to be incorporated into the cyclodextrin ring structure of course it would be much smarter to have oxycodone ibuprofen a universal formulation approach applicable to any molecule such a universal formulation approach to increase the oral bioavailability is micronization, meaning the transfer of drug powders into the size range between typically �� however, nowadays many drugs are oxycodone ibuprofen so poorly soluble that micronization is not sufficient the increase in surface area, and thus consequently in dissolution velocity, is not sufficient to overcome the bioavailability problems of very poorly soluble drugs of the biopharmaceutical specification class ii oxycodone ibuprofen a consequent next step was to move from micronization to nanonization since the beginning of the s, the company nanosystems propagated the use of nanocrystals instead of microcrystals for oral bioavailability enhancement, and also to use nanocrystals suspended oxycodone ibuprofen in water nanosuspensions for intravenous or pulmonary drug delivery the solution was simple in general, simple solutions possess the smartness that they can be realized easier than complex systems and introduction to the market is faster nevertheless, it took about ten years before the first nanocrystals in a tablet appeared on the market, the product rapamune� by the company wyeth in compared with liposomes developed in with the first products on the market around eg oxycodone ibuprofen alveofact�, a lung surfactant, this was still relatively fast what were the reasons that it took about one decade for nanocrystals to enter the market from our point of view, pharmaceutical companies prefer to use formulation technology already oxycodone ibuprofen established with know how available in the company in addition, if formulation technologies are established, a company also has the possibility for production of the final product therefore, all the traditional formulation approaches were exploited to solve a oxycodone ibuprofen formulation problem in addition, formulation approaches were preferred, being even simpler than nanocrystals for example, production of drugcontaining microemulsions administered in a capsule is, in many cases, even simpler another reason for the reluctance of pharmaceutical companies at oxycodone ibuprofen the beginning was the lack of large scale production methods these were not available at the very beginning of the development of the nanocrystal technology meanwhile, this has changed and the major pharmaceutical companies try to secure or have already secured their access to nanocrystal technology access to nanocrystal technology is possible either by licencing in or alternatively by the attempt to develop ones own production technologies for the nanocrystals, which do not depend on oxycodone ibuprofen already existing intelectual property ip this chapter discusses the physicochemical properties of nanocrystals which make them interesting for drug delivery, reviews and discusses briefly the various production methods available and highlights the opportunities for improved drug delivery using oxycodone ibuprofen different application routes definitions drug nanocrystals are crystals with a size in the nanometer range, meaning that they are nanoparticles with a crystalline character there are discussions about the definition of a nanoparticle, referring compare reclast vs boniva injection to the size of oxycodone ibuprofen a particle to be classified as a nanoparticle depending on the discipline, eg in colloid chemistry, particles are only considered as nanoparticles when they are in sizes below nm or even below nm based on the size unit, oxycodone ibuprofen in the pharmaceutical area, nanoparticles should be defined as having a size between a few nanometers and nm im thus, microparticles possess consequently a size micrometer a further characteristic is that drug nanocrystals are composed of drug oxycodone ibuprofen there is no carrier material as in polymeric nanoparticles dispersion of drug nanocrystals in liquid media leads to nanosuspensions, in contrast to micro suspensions or macrosuspensions in general, the dispersed particles need to be stabilized, eg by surfactants oxycodone ibuprofen or polymeric stabilizers dispersion media can be water, aqueous solutions or nonaqueous media [eg liquid polyethylene glycol peg, oils] depending on the production technology, processing of drug micro crystals to drug nanoparticles can lead to either a crystalline oxycodone ibuprofen or to an amorphous product, especially when applying precipitation in the strict sense, such an amorphous drug nanoparticle should not be called nanocrystal however, one often refers to nanocrystals in the amorphous state physicochemical properties of drug nanocrystals oxycodone ibuprofen change of dissolution velocity the reason for micronization is to increase the surface area, thus consequently according to the noyeswhitney equation, increasing the dissolution velocity therefore, micronization can be succesfully employed if the dissolution velocity is the ratelimiting oxycodone ibuprofen step for oral absorption drugs of bsc ii of course, by moving one dimension further to smaller particles, the surface area is further enlarged and consequently, the dissolution velocity is further enhanced in most cases, a low oxycodone ibuprofen dissolution velocity is correlated with a low saturation solubility saturation solubility the general textbook statement is that the saturation solubility cs is a constant depending on the compound, the dissolution medium and the temperature this is valid for oxycodone ibuprofen powders of daily life with a size in the micrometer range or above however, below a critical size of �m, the saturation solubility is also a function of the particle size it increases with decreasing particle size below oxycodone ibuprofen nm therefore, drug nanocrystals possess an increased saturation solubility this has two advantages according to noyeswhitney, the dissolution velocity is further enhanced because dcdt is proportional to the concentration gradient cs � cxh cx � bulk concentration, h oxycodone ibuprofen � diffusional distance due to the increased saturation solubility, the concentration gradient between gut lumen and blood is increased, consequently, the absorption by passive diffusion the interesting question very often asked is how manyfold is the increased saturation solubility?