Pharmaceutical microemulsions, study

For example, SK F-106760 and SK F-l 10679, both water-woluble RGD fibrinogen receptor antagonists, were formulated in microemulsions at pharmaceutically relevant levels, and their uptake after intraduodenal administration was investigated [39-41]. It was found that the presence of the SK F-l 10679 peptide in varying concentrations did not influence the structure of the W/O microemulsion studied. Furthermore, the bioavailability of SK F-106760 was increased dramatically for the microemulsion formulations compared to that of the aqueous solutions, as can be seen in Fig. 5. 

Shukla, A. and Neubert, R.H.H. 2006 Diffusion behavior of pharmaceutical o/w microemulsions studied by dynamic light scattering. Colloid Polym. Sci. 284 568-573. 

In pharmaceutics it is important to know the affinity of drugs to microemulsion. In only a few works were the affinity and the partition behavior of drugs in microemulsions using MEEKC studied (14,32). The partition... 

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

During the late 1990s, Dr. Nastruzzi worked with Professor P. L. Luisi as a postdoctoral fellow at the Institute for Polymers at the Swiss Federal Institute of Technology in Zurich. As a postdoctoral fellow at the Department of Pharmaceutical Sciences at the University of Ferrara, he focused on the production and characterization of liposomes specially designed for retinoid delivery, as well as on biophysical studies and activity of in vitro cultured cell lines. In 1991, he obtained a researcher position in this department, where he devoted his energy to the production of microspheres, liposomes, and microemulsions for the controlled delivery of biological response modifiers. 

Microemulsions are thermodynamically stable isotropic dispersions of oil in water (o/w) or of water in oil (w/o) containing domains of nanometer dimensions stabilized by an interfacial film of surfactant(s). The most typical oil phases are alkanes, the choice of cyclic or aromatic hydrocarbon being dependent on further application. Extensive study of microemulsions has been stimulated by their great potential for practical applications in different fields [1,2] such as pharmaceuticals, cosmetics, enhanced oil recovery and material science (catalysts, semiconductors, etc.). 

Pattarino F, Marengo E, Gasco MR, and Carpignano R. (1993). Experimental design and partial least squares in the study of complex mixtures Microemulsions as drug carriers. International Journal of Pharmaceutics, 91, 157-165. 

Chaiyana W, Rades T, and Okonogi S. (2013). Characterization and in vitro permeation study of microemulsions and liquid crystalline systems containing the anticholinesterase alkaloidal extract from Tabernaemontana divaricata. International Journal of Pharmaceuticals, 452, 201-210. 

Microemulsions as food systems have great potential, which can be attested in patented products (Bauer et al, 2002 Allgaier et al., 2004 Chanamai, 2007). Incorporation of proteins in microemulsions might also have impact in food applications in the future (Rohloff et al., 2003). Studies on microemulsions applied to the pharmaceutical field might also be of interest when seeking food applications, since biocompatible components are used in this field. Studies in this area have been summarized in review articles (Lawrence and Rees, 2000 Rane and Anderson, 2008). 

Nasseria, A.A. et al.. Lecithin-stabilized microemulsion-based organogels for topical application of ketorolac tromethamine. II. In vitro release study. Iranian Journal of Pharmaceutical Research, 2003. 117 123. 

Moreno MA, Ballesteros MP, Frutos P. Lecithin-based oil-in-water microemulsions for parenteral use Pseudoternary phase diagrams, characterization and toxicity studies. Journal of Pharmaceutical Sciences. 2003 92(7) 1428-1437. 

An important aspect in all drug delivery is the toxicity of the drug as well as that of the drug carrier. Therefore, toxicity has to be assessed also for microemulsion formulations. In microemulsion systems, the main concern regarding toxicity has to do with the cosurfactants used. For example, the majority of the work on the pharmaceutical application of microemulsions has involved the use of short- or medium-chain alcohols, e.g., butanol. In a range of studies it has been shown that these cause toxic side effects. For example, inhalation studies of the toxicity of 1-butanol, 2-butanol, and / -butanol in rats showed a dose-dependent reduction in fetal weight [56]. Furthermore, aqueous solutions of ethanol, propanol, and butanol were shown to result in elongated mitochondria in hepatocytes after 1 month of exposure [57]. (In addition to the toxicity aspects of these alcohols, microemulsions formed in their presence are often destabilized on dilution of the continuous phase.) Furthermore, many studies so far have involved aliphatic or aromatic oils, such as hexane or benzene, which obviously are unsuitable for pharmaceutical use. Moreover, ionic surfactants could in themselves be toxic and irritant [58]. 

The wide range of applications and increasing interests on the studies of nonionic surfactant reverse micelles or W/O microemulsions has shown their significance in colloid and polymer sciences. Due to biocompatibilily and biodegradability of the glycerol-based nonionic surfactants, studies on the self-assemblies of these surfactants in polar and nonpolar solvents offer various practical applications in the food, cosmetics, and pharmaceutical industries. 

The search for biodegradable and temperature insensitive microemulsions as various solubilizing and reaction media is of increasing importance for emerging applications in several areas, such as pharmaceutical and medical applications, food products, catalysis, transcriptive syntheses and membrane recognition phenomena, new cosmetic formulations and nanotechnologies. As the medical and pharmaceutical potential of microemulsions needs to be evaluated, the research should be directed not only towards studies of the internal microstructure properties of microemulsions but also at their biological properties such as hemolytic activity and cytotoxicity [1]. 

Cytotoxic effects of the selected microemulsions (Table 1) were measured in MCF-7 cells. The performed cytotoxicity studies demonstrated that only bis(Ci2-LA) allows for near 75% viability of tumor cells. However, presented data reveal that the lactobionic derivative (systems 9,10) is slightly more safe for MCF-7 cells than the gluconic one (systems 7,8). In the presence of microemulsions stabilized with dicephalic (systems 3-6) and single-head single-tail surfactants (systems 1,2), a significant cytotoxic effect was observed. For these reasons, a utility of those systems for pharmaceutical uses should be limited. From the other hand potential applications of the (C12-DX X = GA and LA) systems will be studied for preparation of submicron particles type nanocapsules as useful carriers of the safe drug delivery. Moreover, only systems stabilized by the bis(Ci2-LA) appear to be relatively not toxic for MCF-7 breast cancer cells. Thus microemulsions stabilized by this surfactant may be used in... 

Saint-Ruth, H., Attwood, D., Ktistis, G., and Taylor, C. J. 1995. Phase studies and particle size analysis of oil-in-water phospholipid microemulsions. International Journal of Pharmaceutics, 116, 253-261. 

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