Microemulsions pharmaceutical applications

Patravale, V.B., and Date, A.A. (2009) Microemulsions pharmaceutical applications, in Microemulsion Background, New Concepts, Applications, Perspective (ed. C. Stuhenrauch), John Wiley Sons, Ltd, Oxford, p. 259. 

Tenjarla, S., Microemulsions an overview and pharmaceutical applications, Crit. Rev. Then Drug, 16, 461, 1999. 

Leung, R. and D. O. Shah (1989). Microemulsions an evolving technology for pharmaceutical applications. In Rossof, M. (ed.)Qontrolled Release of Drugs Polymers and Aggregate Sy t 8W, New York, pp. 85-215. 

Microemulsion system applications span many areas including enhanced oil recovery, soil and aquifer decontamination and remediation, foods, pharmaceuticals (drug delivery systems), cosmetics, and pesticides [2,5,33,37,232,233]. Some of these are listed in Table 3.6. The widespread interest in microemulsions and use in these different industrial applications are based mainly on their high solubilization capac-... 

Tenjarla, S. Microemulsions An overview and pharmaceutical applications. Critical reviews in therapeutic drug carrier systems. 1999, 16, 461-521. 

Tenjarla S. Microemulsions An Overview and Pharmaceutical Applications. Grit Reviews in TherDrug Carrier Sys 1999 16 461-521. 

Considerable research is being done to increase the utility of CO2 as a solvent. In the area of pharmaceutical applications, supercritical fluids are useful as solvents in the production of particulate drugs, the extraction and separation of active ingredients, and the preparation of microemulsions and sustained drug delivery systems (2). A major disadvantage, insofar as solvent... 

The phenomenon of microemulsification is mainly governed by factors such as (1) nature and concentration of the oil, surfactant, co-surfactant and aqueous phase, (2) oil/surfactant and surfactant/co-surfactant ratio, (3) temperature, (4) pH of the environment and (5) physicochemical properties of the API such as hydrophilicity/lipophilicity, plformulating microemulsions. From a pharmaceutical perspective, one of the most important factors to be considered is acceptability of the oil, surfactant and co-surfactant for the desired route of administration. This factor is very important while developing micro emulsions for parenteral and ocular delivery as there is only limited number of excipients which are approved for the parenteral and ocular route. In Chapter 3 of this book a more general overview of formulating microemulsions is given and formulation considerations with respect to the components of microemulsions used in pharmaceutical applications are discussed below. 

For medical or pharmaceutical applications, attention must be paid to the problems that can be caused by the possible toxicity of the surfactant remaining in the final product. Antonietti et al. [89] proposed the use of natural, nontoxic, and nondenaturing surfactants based on mixtures of lecithin and sodium chlolate for the formation of globular microemulsions. Pure lecithin is known to form bilayers or liposomes. The role of sodium cholate is to increase the curvature and flexibility of the interfacial layer, allowing the formation of small droplets. The final microlatex particles have a size ranging from 22 to 40 nm, depending on surfactant composition and concentration. The ability to functionalize the surface of these particles was demonstrated by the incorporation of protein molecules. 

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]. 

There is a lot of interest in microemulsions as is shown by this book [94] and by recent pubHcations on microemulsion models [95, 96], as well as oil chain length dependence [97] and the use of poly(ethylene glycol) (PEG) and microemulsions for pharmaceutical purposes [98, 99]. Microemulsions are used in many industrial appHcations [100], especially within the area of cosmetics and detergents [101] as well as in pharmaceutical applications [102] one of the more important ones being as drug-delivery systems [103-112]. 

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