Nanoemulsions formulation

Ganta, S. and Amiji, M. (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Molecular Pharmacology, 6 (3), 928-939. Sonneville-Aubrun, O., Simonnet, J.-T. and L Alloret, F. (2004) Nanoemulsions a new vehicle for skincare products. Advances in Colloid and Interface Science, 108-109, 145-149. 

Wang L., Li, X., Zhang, G., Dong, J. and Eastoe, J. (2007) Oil-in-water nanoemulsions for pesticide formulations. Journal of Colloid and Interface Science, 314, 230-235. 

Anton, N., Benoit, J.P. and Saulnier, P. (2008) Design and production of nanopartides formulated from nanoemulsion templates - a review. Journal of Controlled Release, 128, 185—199. 

Patents have been granted for innovations involving the preparation and activities of broad-spectrum antimicrobial emulsions from 1977 (Sippos) to 2000 (Baker). All of these patents claim antibacterial activity, but all involve additives in the non-aqueous phase of the emulsion that are known to be antibacterial alone and before emulsification. Wide spectrum applications for these nanoemulsions have been claimed with positive results for bacteria, fungi, and viruses. The term nanoemulsion is used in US patents discussed below, but the generic term for the product of an emulsification (Gooch 2002, 1980) of a liquid within a liquid is an emulsion. United States patents 6,015,832 and 5,547,677 were examined and formulations in key claim statements were reproduced, and tested using standard methods for effectiveness. Additional patents listed in the reference section were reviewed as part of this study. 

Santos-Magalhaes et al. [27] reported on PLGA nanocapsules/nanoemulsions for benzathine pencillin G. Nanoemulsions were produced by spontaneous emulsification and nanocapsules by interfacial deposition of the pre-formed polymer. They have observed similar release kinetics from both formulations [27]. 

In pharmaceutical preparations, soybean oil emulsions are primarily used as a fat source in total parenteral nutrition (TPN) regimens. Although other oils, such as peanut oil, have been used for this purpose, soybean oil is now preferred because it is associated with fewer adverse reactions. Emulsions containing soybean oil have also been used as vehicles for the oral and intravenous administration of drugs drug substances that have been incorporated into such emulsions include amphotericin, " diazepam, retinoids, vitamins, poorly water-soluble steroids, fluorocarbons, and insulin. In addition, soybean oil has been used in the formulation of many drug delivery systems such as liposomes, microspheres, dry emulsions, self-emulsifying systems, and nanoemulsions and nanocapsules. ... 

Hatanaka et al. (2008) examined a number of different types of encapsulation systems for coenzyme Qio- Systems examined included a novel liquid nanoemulsion and water-soluble powder formulations, acyclodextrin inclusion complex, and a dry emulsion. Of the delivery systems examined the novel nanoemulsion delivery system, which had the smallest particle size (60 nm) compared to the other delivery systems examined (770-2400 nm), had the highest bioavailability when tested in rat models (Hatanaka et al., 2008). 

Several classes of formulations of disperse systems are encountered in the chemical industry, including suspensions, emulsions, suspoemulsions (mixtures of suspensions and emulsions), nanoemulsions, multiple emulsions, microemulsions, latexes, pigment formulations, and ceramics. For the rational preparation of these multiphase systems it is necessary to understand the interaction forces that occur between the particles or droplets. Control of the long-term physical stability of these formulations requires the application of various surfactants and dispersants. It is also necessary to assess and predict the stability of these systems, and this requires the application of various physical techniques. 

Since the gravity force is proportional to R, then if R is reduced by a factor of 10, the gravity force is reduced by 1000. Below a certain droplet size (which also depends on the density difference between oil and water), the Brownian diffusion may exceed gravity and creaming or sedimentation is prevented. This is the principle of formulation of nanoemulsions (with size range 20-200 nm) that may show very little or no creaming or sedimentation. The same applies for microemulsions (size range 5-50 nm). 

Nanoemulsions can be applied for the dehvery of fragrants, which are often incorporated in many personal care products. The same could apply to perfumes, which preferably are formulated alcohol-free. 

A lack of understanding of the interfacial chemistry involved in production of nanoemulsions. For example, few formulations chemists are aware of the concepts of phase inversion composition (PIC) and phase inversion temperature (PIT), and how these can be usefuUy apphed to produce small emulsion droplets. 

In spite of the above difficulties, several companies have introduced nanoemulsions onto the market, and their benefits will be evaluated within the next few years. Nanoemulsions have been used in the pharmaceutical industry as drug-delivery systems [5], although the acceptance by customers of nanoemulsions as a new type of formulation depends on how they are perceived and their efficacy. With the advent of new instruments for high-pressure homogenisation, and the competition between various manufacturers, the cost of nanoemulsion production wiU surely and may even approach that of classic macroemulsions. Fundamental investigations into the role of surfactants in the process [6,7] will lead to optimised emulsifier systems such that a more economic use of surfactants will doubtless emerge. 

CDC are defined only by their size (most scientists agree on sizes below 1 pm others set 0.5 pm as the upper limit). CDC are very heterogeneous in all other aspects (e.g., thermodynamic stability, chemical composition, and the physical state, including solid, liquid, or liquid-crystalline dispersions) [ 1 ]. The most prominent examples are nanoparticles, nanoemulsions, nanocapsules, liposomes, nanosuspensions, (mixed) micelles, microemulsions, and cubosomes. Some CDC have reached the commercial market. Probably the best known example is the microemulsion preconcentrate of cyclosporine (Sandimmun-Neoral), which minimized the high variability of pharmacokinetics of the Sandimmun formulation. In addition, intravenous injectable CDC have been on the commercial market for many years. Examples include nanoemulsions of etomidate (Etomidat-Lipuro) and diazepam (Diazepam-Lipuro) [2-4], mixed micelles (Valium-MM, Konakion), and liposomes (AmBisome) [5]. 

These cationic SLN are formulated from a matrix lipid surfactants to stabilize the formulation and cationic lipids to charge the SLN surface positively. The cationic lipids employed are the same used in cationic liposomes for transfection [28]. Eormulation optimization studies revealed that both the cationic lipid and the matrix lipid influence transfection activity [27]. Comparable results were found for the oil component in cationic nanoemulsions for transfection [29]. Several formulations made from different cationic lipids and matrix lipids were tested for in vitro transfection efficiency (Eigure 6.8). The SLN Cp DOTAP made from the wax cetyl pahnitate and the cationic lipid N-[l-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium... 

Uwari SB and Amiji MM (2006) Improved oial delivery of paclitaxel following administration in nanoemulsion formulations. J. Nanosci. Nemotech. 6 3215-3221. 

Vyas, T.K., A. Shahiwala, and M.M. Amiji. 2008. Improved oral bioavailabiUty and brain transport of saquinavir upon administration in novel nanoemulsion formulations. Int. J. Pharm. 347(l-2) 93-101. 

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