ABSTRACT
Microemulsions are transparent colloidal assemblies that have polar and nonpolar microdomains. They consist either of water droplets in oil or oil droplets in water where the droplets are surrounded by surfactant lm, or they have abicontinuous microstructure, i.e., continuous channels of oil and water separated by the surfactant. Due to their thermodynamic stability, these systems have good shelf life, large surface area, low viscosity, and ultralow surface tension (Hoar and Schulman 1943, Prince 1977, Danielsson and Lindman 1981, Bourrel and Schecter 1988, Sjoblom et al. 1996, Kunieda and Solans 1997, Paul and Moulik 1997, Moulik and Paul 1998, Salager and Anton 1999, Fanun 2009a). The formulation and characterization of microemulsions was extensively investigated(Kahlweit et al. 1996, Tlusty and Safran, 2000, Tlusty et al. 2000, Hellweg 2002, Salager et al. 2005). Due to the existence of polar, nonpolar, and interfacial microdomains, microemulsion systems operate as excellent solvents of active ingredients, including drugs that are relatively insoluble in both aqueous and organic solvents (Kreuter 1994, Paul and Moulik 2001, Flanagan and Singh 2006, Kogan and Garti 2006, Gupta and Moulik 2008, Fanun 2010). Due to their special physicochemical properties, such as in the nanometer range of controlled drop size, the almost monodisperse size distribution, alarge specic inner surface, and adistinctive dissolving power for reactants, they are of interest for a number of industrial processes. Enhancing solubilization in microemulsions is directly related to the presence of asmooth, blurred, and expanded transition across the interfacial region from polar to apolar bulk phases (Salager et al. 2005). Improved solubilizationin microemulsions could be achieved by the addition of polar oil through the so-called lipophilic linker effect. The best lipophilic linker was found to have ahydrophobe chain length as an average between that of the surfactant tail and the oil (Salager et al. 1998). Lipophilic linkers are sometimes added to oil-water-ionic surfactant microemulsions in order to increase the solubilizationof hydrophobic oils (Szekeres et al. 2006). The development of novel microemulsions to be used as biocompatible nanomaterial for biomedical and pharmaceutical applications, to improve the quality of the already existing medical devices has assumed great importance. The relationship between the structural features of biocompatible microemulsions and drug solubilization and delivery was studied (Dalmora et al. 2001, Carlotti et al. 2003, Formariz et al. 2007, 2008). Biocompatible microemulsions are qualied to be prospective drug delivery systems, provided they are composed of biocompatible excipients (Das et al. 1991, Paul and Moulik 1991, Mitra et al. 1994, Constantinides
18.1 Introduction .......................................................................................................................... 417 18.2 Microemulsions Based on Cyclic Oils.................................................................................. 419 18.3Microemulsions Based on Linear Oils ................................................................................. 421 18.4Microemulsions Based on Mono-, Di-, and Triglycerides .................................................... 422 18.5Summary ..............................................................................................................................424 Symbols and Terminology ............................................................................................................. 425 References ...................................................................................................................................... 425
1995, Mitra et al. 1996, Tenjarla 1999, Acharya et al. 2001a,b, Mele et al. 2004, Acosta et al. 2005, Mitra and Paul 2005). Biocompatible microemulsions have also been found to improve the bioavailabilityof certain drugs, e.g., orally administered labile peptides and proteins (Sarciaux et al. 1995, Mitra et al. 1996, Majhi and Moulik 1999, Watnasirichaikul et al. 2000, 2002, Radwan and AboulEnein2002, Krauel et al. 2005, Pinto-Reis et al. 2006, Graf et al. 2009). For example, contact lenses made of microemulsion-laden gels are expected to deliver drugs at therapeutic levels for a few days. The delivery rates can be tailored by controlling the particle and the drug loading (Le Bourlais et al. 1998, Arriagada and Osseo-Asare 1999, Gulsen and Chauhan 2005). Doxorubicin biocompatible oil-in-water (O/W) microemulsions stabilized by mixed surfactants containing soya phosphatidylcholinewere reported by Formariz et al. (2006). The characterization of caprylocaproyl macrogolglycerides-based microemulsion drug delivery vehicles for an amphiphilic drug was studied by Djordjevic et al. (2004). Other authors reported (Monduzzi et al. 1997, Rohloff et al. 2003, La Mesa 2005, Shimek et al. 2005, Gochman-Hecht and Bianco-Peled 2006, Zimmerberg and Kozlov 2006, Kim and Dungan 2008) on the ability of water-soluble, globular proteins to tune surfactant/oil/water self-assemblies and their potential for the formation of microemulsions for biological applications. The use of microemulsions for the delivery of proteins and nutraceuticals was also reported (Pauletti et al. 1996, Watnasirichaikul et al. 2000, 2002, Eaimtrakarn et al. 2002, Pitaksuteepong et al. 2002, Radwan and Aboul-Enein 2002, Djordjevic et al. 2004, des Rieux et al. 2006, Pinto Reis et al. 2006, Spernath and Aserin 2006). Microemulsions composed of £uorinated oil with abiocompatible hydrogenated surfactant were investigated as blood substitutes (Cecutti et al. 1989, 1990). Microemulsions were also used for the preparation of poly(alkylcyanoacrylate) nanoparticles (Watnasirichaikul et al. 2000, Krauel et al. 2005, 2006). Methylene blue (MB)-doped silica nanoparticles(NPs) were prepared in areverse microemulsion and used as anovel matrix for biochemical application (Watnasirichaikul et al. 2000, Krauel et al. 2005, 2006). Abiocompatible microenvironmentwas provided for heme proteins retaining their native conformation and biological activity by the silica matrix with hydrophilic groups (Bagwe et al. 2004, Zhao et al. 2004, Xian et al. 2006). Studies on biocompatible nanocapsules formed in microemulsion-templated processes were also reported (Zieliñska et al. 2008). Microemulsions along with other systems have been used as precursorsfor the synthesis of encapsulating agents (Cortesi and Nastruzzi 1999, Couvreur et al. 2002, Chávez et al. 2005). Biocompatible microemulsions were used for the formation of organogels (Luisi et al. 1990, Angelico et al. 2005), and in the design and production of skin care products, which are nowadays dened by terms like quality, safety, efcacy, exclusiveness, and consumer condence (Magdassi and Touitov 1998, Gasperlin and Kristl 2000). Anumber of studies were conducted on the formulation and characterization of pseudoternary biocompatible systems containingsurfactants (single or mixed), cosurfactant(s), oil (single or mixed), and water (Das et al. 1991, Paul and Moulik 1991, Mitra et al. 1994, 1996, Constantinides 1995, Tenjarla 1999, Acharya et al. 2001a,b, Shukla et al. 2002, Mele et al. 2004, Mitra and Paul 2004, 2005, Acosta et al. 2005). The in£uence of surfactant types along with their chain lengths, structure and mixing ratios, type of cosurfactants and oils on the extent of the one-phase microemulsions region in the phase diagramshas been investigated (Leung and Shah 1987, Kunieda and Aoki 1996, Kumar and Mittal 1999, Evans and Wennerstrom 1999). The formation of microemulsion using biocompatible sucrose alkanoate systems was reported (Kunieda and Shinoda 1985, Herrington and Sahi 1988, Pes et al. 1996, Aramaki et al. 1997a, Nakamura et al. 1997, 1999). Microemulsions are useful as reaction media as away to overcome the reactant incompatibility problem that one frequently encounters in organic synthesis. The use of amicroemulsion can be seen as an alternative to phase-transfer catalysis. Holmberg (2007) reported on the usefulness of microemulsions for overcoming reactant incompatibility, speeding up reactions of one polar and one apolar reactant, and inducing regiospecicity. The use of water-in-oil (W/O) microemulsions as medium for enzymatic reactions is apromising application. Microemulsions were also extensively tested for their potential for this application (Avramiotis et al. 1999, Klier et al. 2000, Garti 2003, Bauduin et al. 2005, Garti et al. 2005, Papadimitriou et al. 2005, 2007). The enzyme efciency was affected by the chain length of the
surfactant and the nature of the cosurfactant used in the formulation of the biocompatible microemulsions as reported (Stamatis and Xenakis 1999, Stamatis et al. 1999, Zhou et al. 2001, Fadnavis and Deshpande 2002, Matura et al. 2002, Orlich and Schomacker 2002, Garti 2003, Flanagan and Singh 2006, Leser et al. 2006, Papadimitriou et al. 2007, 2008). The solubilization of polar oils in surfactant self-organized structure was investigated by small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS) (Barlow et al. 2000, Kunieda et al. 2001). The formation of middle-phase microemulsions of polar oils was reported (Nishimi 2008). This chapter will review on the development and characterization of biocompatible microemulsion systems and their evaluationas probable vehicles for encapsulation, stabilization, and delivery of bioactive natural products and prescription drugs. The review will be based on the classication of microemulsions according to the type of oil used in its formulation. The types of oils that will be reviewed are mainly the polar ones that include cyclic £avors, linear esters, and mono-, di-, and triglycerides.
