Nanodispersions

Many water insoluble drugs are formulated as nanodispersions, namely nanoemulsions and nanosuspensions. These systems enhance the bioavailability of insoluble drugs, whereby reducing the droplet or particle size to nanoscale dimensions increases the solubility of the drug. This can be clearly understood if one considers the effect of size on solubility as given by the Kelvin equation [10] 

Many lipophilic drugs are formulated as oil-in-water (0/W) nanoemulsions. The drug may be an oil with low viscosity which can be directly emulsified in water using a surfactant such as lethicin or castor oil ethoxylate. For viscous drug oils, the latter 

To prepare an emulsion oil, water, surfactant and energy eue needed. This can be understood from a consideration of the energy required to expand the interface, AAy (where AA is the increase in interfacial area when the bulk oil with area A produces a large number of droplets with area A, y is the interlacial tension). Since 

Y is positive, the energy to expand the interface is large and positive. This energy term cannot be compensated by the small entropy of dispersion TAS (which is also positive) and the total free energy of formation of an emulsion, AG is positive. 

A is the wavelength of light in vacuo, n is the refractive index of the solution and 0 is the scattering angle. 

Although many areas of nanotechnology do not directly deal with colloidal dispersions (such as nanoelectronic devices [952]) other areas do, such as the use of colloidal ink dispersions in robocasting to build near-nanometre scale three-dimensional structures. The possible use of nanoemulsions for intravenous delivery and in medical diagnostics has already been mentioned in Sections 14.4 and 14.5. Some other application areas include  

Due to their extremely small size and correspondingly large surface areas, nanoparticle suspensions have potential applications in such areas as  

W/O microemulsions have been used in the preparation of nanopartides and for carrying out other reactions in highly confined geometries [234], As mentioned in Section 14.3 both nanoparticle suspensions and nanoemulsions have developed for use as drug-delivery agents. 

Nanosheets as thin as a few atoms have been prepared from pyrolytic graphite. These graphene sheets are typically made up of hexagonally oriented carbon atoms, are a few nm in thickness, and have been prepared in diameters of lOs-lOOs of (J,m 

Nanotubes can be filled with other chemical species, including water molecules. This has been achieved using ABA triblock copolymers to create soft-walled polymer 

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Dubau L. 2002. Electrocatalyseurs platine-mthenium nanodisperses pour une pile a combustion directe de methanol. PhD Thesis, University of Poitiers, Prance. 

H Ibrahim, C Bindschaedler, E Doelker, P Buri, R Gurny. Aqueous nanodispersions prepared by a salting-out process. Int J Pharm 87 239-246, 1992. 

E Allemann, R Gurny, E Doelker. Preparation of aqueous polymeric nanodispersions by a reversible salting-out process, influence of process parameters on particle size. Int J Pharm 87 247-253, 1992. 

Many synthetic methods for the preparation of nanodispersed material have been reported, several routes applying conventional colloidal chemistry, with others involving the kinetically controlled precipitation of nanocrystallites using organometallic compounds.3 6-343 Controlled precipitation reactions yield dilute suspensions of quasi-monodispersed particles. This synthetic method sometimes involves the use of seeds of very small particles for the subsequent growth of larger ones.359 360... 

This method of nanodispersed metal production has the advantages as compared with the previous one because metal reduction is performed at sufficiently low temperatures (20-200°C). That is why the diffusion of atoms and migration of the formed metal particles is suppressed, no metal particles agglomeration occurred. 

The reprecipitation strategy lies in the conversion of the products dissolved in a suitable organic solvent into nanodispersed systems in a different medium by a precipitation/condensation procedure. On the other hand, the ion-association strategy can produce ion-based dye nanoparticles in pure aqueous media by utilizing a water-insoluble ion-pair formation reaction. The following example shows the size-dependent absorption properties for the cation-based pseudoisocyanine (PIC see the chemical structure in Fig. 4) dye nanoparticles. 

SLN for the topical application to the skin are made np from lipids such as glyceryl behenate (Compritol 888 ATO), glyceryl monostearate (Imwitor 900), glyceryl pahnitostearate (Precirol ATO 5), triglycerides (trimyristin, tripalmitin, tristearin), or the wax cetyl pahnitate. Nanodispersions contain 5 to 40% lipid the higher-concentrated preparations have a semisolid appearance. These nanodispersions are cosmetically acceptable as they are, whereas the fluid nanodispersions with lower lipid content shonld be incorporated into, for example, a cream that facilitates the application. 

Lipid nanodispersions (SLN and NLC) are complex, thermodynamically unstable systems. The colloidal size of the particles alters physical features (e.g., increasing solubihty and the tendency to form supercooled melts). The complex structured lipid matrix may include hquid phases and various lipid modifications that differ in the capacity to incorporate drugs. Lipid molecules of variant modifications may differ in their mobility. Moreover, the high amount of emulsifier used may result in liposome or micelle formation in addition to the nanoparticles. 

Therefore, extensive characterization is required, as the physicochemical properties of lipid nanodispersions influence not only drug incorporation and release but also the physical stability of the preparation for example, drug localization in the matrix. Several methods have to be combined for characterization to allow detection of dynamic processes such as changes in lipid modifications, particle aggregation, and the formation of nanostructures of other kinds. 

INCORPORATION OF LIPID NANODISPERSIONS INTO DERMATICS FOR TOPICAL USE... 

The generally low lipid content and the poor viscosity of lipid nanodispersions make these preparations, as they are, less suitable for dermal drug application. The handling of the preparation by the patient is improved by SLN incorporation into ointments, creams, and gels. Alternatively, ready-to-use preparations may be obtained by one-step production, increasing the lipid phase to at least 30%. However, increasing the lipid frequently results in an unwanted increase in particle size. Surprisingly, it has been found that very concentrated (30 to 40%) semisolid cetyl palmitate formulations preserve the colloidal particle size [10]. 

Following the evaporation of water from the lipid nanodispersion applied to the skin surface, lipid particles form an adhesive layer, applying occlusion to the surface [17,40]. Therefore, the hydration of the stratum comeum may increase, which can facilitate drug penetration into deeper skin strata and even systemic availability of the drug. Occlusive effects are strongly related to particle size. Nanoparticles have turned out 15-fold more occlusive than microparticles [17], and particles smaller than 400 nm in a dispersion containing at least 35% high-crystallinity lipid proved to be most potent [41]. 

Nonloaded and loaded SLN were already investigated with respect to use in cosmetics. Although adequate controls are difficult to prepare, first experiments indicate an increase in skin hydration and a reduction in wrinkle depth following SLN application [68]. Moreover, cetyl palmitate-nanodispersions act both as particulate ultraviolet (UV) blockers themselves and as carriers for UV absorbing agents (e.g., 2-hydroxy-4-methoxy benzophenone Eusolex 4360). This results in a threefold... 

Very thin (average diameter 10 nm) and thin (average diameter 40 nm) H-CNFs were obtained in a highly dispersed form using nanodispersion equipment (T.K. FILM ICS Model 56-50, Primix, Japan) to undo the entangled network with an impeller... 

The single cell performance and the maximum power density of the Pt-Ru 40 wt% catalyst supported on thin H-CNF are shown in Figure 3.8. The maximum power densities were 76, 140 and 246mWcm at 30, 60 and 90°C, respectively. The present nanodispersion treatment is therefore very effective in dispersing thin CNFs. 

Table 3.5 compares the maximum power densities of the catalysts supported on very thin and thin H-CNFs following the nanodispersion procedure described above. Nanodispersion seems to be effective in improving the power density for thin H-CNF-supported catalysts, probably due to an increased number of supporting... 

The catalyst impregnation on the dispersed CNFs must be carefully optimized to obtain a sufficient dispersion of noble metals. Dispersion ofthe CNF in the particular solvent is desirable for uniform impregnation ofthe catalyst. CNFs with very small diameter are very important for effective dispersion. Sophisticated procedures for dispersion must be applied. In the present study, nanodispersion at an impeller agitation of 16 500 rpm was applied to disperse the thin CNFs better. 

Addition of nanodispersed SiO decreased the formation of mesopores (Fig. 4.5). Addition of 5% of SiO preserved the volume of micropores, while the volume of mesopores reduced four-fold. In this case the formation of mesopores was possibly... 

Fig. 4.5 Effect of adding SiO nanodispersion on the pore size distribution in products of polymer dehydrochloiination. 1 - initial sample 2 - with 5% of SiO 5 - with 25% of SiO...

Kosaraju et al., 2006), as well as to encapsulate probiotic cultures (Fei-joo et al., 1997) and to make vitamin E nanoparticles (100 nm) stabilized by a starch coating suitable for fortified beverages (Chen and Wagner, 2004). And, by using microfluidization followed by solvent evaporation, Tan and Nakajima (2005) have reported preparation of (3-carotene nanodispersions (60-140 nm). 

Ribeiro, H.S., Chu, B.S., Ichikawa, S., Nakajima, M. (2008). Preparation of nanodispersions containing P-carotene by solvent displacement method. Food Hydrocolloids, 22, 12-17. 

Tan, C.P., Nakajima, M. (2005). fi-Carotene nanodispersions preparation, characterization and stability evaluation. Food Chemistry, 92, 661 -671. 

Karavas, E., G. Ktistis, A. Xenakis, and E. Georgarakis. 2006. Effect of hydrogen bonding interactions on the release mechanism of felodipine from nanodispersions with polyvinylpyrroliBand.Pharm Biopharm63 103-114. 

J. A. Bouwstra, O. Sibon, M. A. Salomons-de Vries, F. Spies. Interactions between nanodispersions and human skin, Proceedings of the Controlled Rel. Society Meeting, Orlando, 1992, pp. 481-482. 

Figure 3.40 Oxidation of Co on nanodispersed Au particles on metal oxide catalyst carriers as a function of temperature 20 000 h"1 GHSV feed, 1% CO, 20% 02, 4% Ar, 75% He [67],...

Microstructures of (1) PE-g-PPG polymer hybrid and (2) the blended sample of PE and PPG were observed by transmission electron microscopy (TEM) images after the preparation of press sheets of each polymer sample at 200 °C. The TEM images of the resulting polymer hybrid reveal the nanometer level microphase-separation morphology between the PE segment and the PPG segment compared with the PE/PPG blended polymer. From the result, the nanodispersion of different segments in polymer hybrids is possible, but different from the blended polymer sample (Fig. 8). 

If the nanodispersed species have sizes of the order of 10 nm, diagnostic agents encapsulated in such nanoparticles could potentially cross into human cells. For example, 10 nm diameter, silica-coated, cadmium selenide crystals have been able to transfer into vesicles and be transported by them [901], These protein-sized particles fluoresce for long periods of time making them potentially useful for diagnostic labelling. 

There are also some new trends emerging in areas that might not have been fully appreciated as recently as ten years ago. Three examples are smart colloids, nanodispersions, and the need to combat agents of terror. 

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