Surfactants pharmaceutical applications

Florence (1983) provide a comprehensive reference for the use of surfactants in drug formulation development. The treatment by Florence (1981) of drug solubilization in surfactant systems is more focused on the question at hand and provides a clear description of surfactant behavior and solubilization in conventional hydrocarbon-based surfactants, especially nonionic surfactants. This chapter will discuss the conventional surfactant micelles in general as well as update the reader on recent practical/commercial solubilization applications utilizing surfactants. Other uses of surfactants as wetting agents, emulsiLers, and surface modiLers, and for other pharmaceutical applications are nc emphasized. Readers can refer to other chapters in this book for details on these uses of surfactant Polymeric surfactant micelles will be discussed in Chapter 13, Micellization and Drug Solubility Enhancement Part II Polymeric Micelles. 

The experimentally derived empirical expressions used in models such as the mass-action framework have contributed greatly to the logical selection of surfactants for efLcient and effective solubilization of drugs. However, there is currently a need to develop more efLcient, less toxic surfactants for use in drug delivery. A model that is able to provide quantitative prediction of the critical micelle concentration and micelle size without the need for extensive experimental measurements would greatly accelerate the development of novel surfactant chemistries for use in pharmaceutical applications. 

Gadelle et al. (1995) investigated the solubilization of various aromatic solutes irbfftRSS-b-PEO (ABA)/PPO-bPEO-bPPO (BAB) triblock copolymers. According to the experimental results, they indicated two different solubilization processes. To understand better the mechanism for solubilization in the polymeric surfactant solutions, it was postulated that (1) the addition of apolar solutes promotes micellization of the polymeric surfactant molecules, (2) the central core of the polymeric micelles contains some water molecules, and (3) solubilization is initially a replacement process in which water molecules are displaced from the micellar core bythesolubilizate. Adetailed discussion of the solubilization process can be found in the next section and the pharmaceutical application section of this chapter. 

A.G. Volkov, Ed., Liquid Interfaces in Chemical, Biological and Pharmaceutical Applications, Marcel Dekker, New York, 2001, Surfactant Science Series, Vol. 95. 

Major polymer applications pharmaceutical applications, controlled release drugs,. polyester fibers, unsaturated polyester resins, oil exploration, polyols, surfactants, haircare, switching elements, polymer electrolytes, lithium batteries, nanocomposites... 

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. 

The use of substances that due to their ability to form structural-mechanical barrier are capable of very strong stabilization of emulsions (and especially of concentrated ones), allows one to prepare many commercial emulsions that are used e.g. in emulsion polymerization [55], lubricantcooling liquids, etc. Such surfactants, and especially natural ones, are widely used in food and pharmaceutical applications [56-58]. These surfactants are, for instance, formed as a result of chemical reaction between dextrins and their derivatives (generated by thermal decomposition and partial oxidation of starch) and oils. 

M Partenskii, P Jordan. In AG Volkov, ed. Liquid Interfaces in Chemical, Biological, and Pharmaceutical Applications, vol. 95 of Surfactant Science Series. New York Marcel Dekker 2001, pp 51-82. 

The surfactant must be nontoxic for using pharmaceutical applications. 

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]. 

Complex Formation of Surfactants with Aromatic Compounds and their Pharmaceutical Applications... 

As mentioned in Chapter 1, there can be thousands of molecules with polar heads and nonpolar tails, usable as surfactants. The applications are also many. Thus, the commercial anionic surfactants, recording about 50% of all surfactant production, are literally used all over the place shampoos, dishwashing detergents and washing powders are some common examples. Cationic surfactants likewise are used in hair-conditioners, fabric softeners, asphalt coating, corrosion inhibitor formulations for metal surfaces etc. The major applications of non-ionic surfactants are in the areas of food and drinks, as also pharmaceuticals and cosmetics. Amphoteric /zwitterionic surfactants have only limited applications one area is cosmetics, especially skin care products. 

The worldwide annual production of all alkylphenols exceeds 1 billion pounds. The direct use of alkylphenols is, however, limited to only a few minor applications. The vast majority of alkylphenols are used as intermediates in the synthesis of derivatives, which (in turn) have a wide range of applications ranging from surfactants to pharmaceuticals. The principal markets for alkylphenols are nonionic surfactants, lube-oil additives, phenolic resins, polymer additives, and agrochemicals. The alkylphenols that are most significant in surfactant and applications, along with their general mode of manufactme and other major commercial applications are... 

Ghebremeskel A, Vemavarapu C et al (2007) Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API selection of polymer-surfactant combinations using solubility parameters and testing the processability. Int J Pharm 328(2) 119-129 Gogos C, Liu H (2012) Laminar dispersive and distributive mixing with dissolution and applications to hot-melt extrusion. In Douroumis D (ed) Hot-melt extrusion pharmaceutical applications. Wiley, New York, pp 261-284... 

The understanding of the interfacial behavior of aqueous surfactant solutions is a major issue in surface science both from a theoretical and from a technological point of view. On the one hand, the interpretation of several colloid phenomena requires detailed knowledge of the adsorption layer of the system [1] on the other hand, the performance of many commercial products and industrial technologies (e.g. detergents, pharmaceutical applications, food and mineral processing, oil recovery) [2] is based on the adsorption of surfactant molecules. This explains the widespread interest in surfactant adsorption studies and the fact that this phenomenon is still the subject of intensive experimental and theoretical investigation [3]. 

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