Solubilizing agents cyclodextrins

Unfortunately, the relatively low solubility of /8-cyclodextrin has precluded its widespread use as a solubilizing agent. To enhance the solubility of /8-cyclodextrin, much work has been carried out on possible derivatizations of the /8-cyclodextrin skeleton. 2-Hydroxypropyl-/3-cyclodextrin has been found to exhibit the desired enhanced solubility, while still retaining the optimal binding characteristics of underivatized /8-cyclodextrin. In addition, this derivative is relatively nontoxic and may even be used in parenteral applications [63],... 

V. M. Rao, J. L. Haslam, and V. J. Stella. Controlled and complete release of a model poorly water-soluble drug, prednisolone, from hydroxypropyl methylcelluose matrix tablets using (SBE)7m-P-cyclodextrin as a solubilizing agent. J. Pharm. Sci. 90 807-816, 2001. 

Retinoids were used also in our subsequent work on cyclodextrins. 3-cyclodextrin has rather low water solubility and that limits its ability to form soluble complexes and is probably also the cause of its toxicity when applied parenterally. We previously had a good experience with 2,6-0-dimethy1-3-cyclodextrin as a solubilizing agent consequently we wanted to continue with that compound and introduce it into biotests we had available (5). The preparation and structure of 2,6-0-dimethy1-3-cyclodextrin is illustrated in the scheme below. The problem of... 

Cyclodextrins, on the other hand, are used extensively in cosmetic and drug delivery applications (132-136). Cyclodextrins, as the name implies, are cyclic amyloses comprised of 6 (a-), 7 (P-), and 8 (y-), a-D-(l,4)-glucose monosaccharides (Fig. 30). Their small size classifies them as oligo- instead of polysaccharides, which places them somewhat outside the scope of this chapter. Nevertheless, cyclodextrins are important components in many cosmetic formulations where they function as hosts and solubilizing agents for water-sensitive or water-insoluble materials. 

Hydrogenolysis of water-insoluble aryl halides in neat water can also be aided by such solubilizing agents as cyclodextrins. An electrocatalytic process of dechlorination of chloroorganic pollutants in the presence of supported Pd in water has been describedJ ... 

Despite the relatively good results found in literature for soil contaminated with TCE, the removal and elimination of COCs requires enhanced electrokinetic technologies. They comprise the use of solubilizing agents such as cosolvents, surfactants, or cyclodextrins. The other possible alternative for the removal of COCs from soil implies the combination of electrokinetic with other remediation techniques such as chemical and electrochemical oxidation/reduction, permeable reactive barriers, electrolytic barriers, and electric heating. 

Duan, M. S., Zhao, N., Oessurardottir, I. B., Thorsteinsson, T., and Loftsson, T. 2005. Cyclodextrin solubilization of the antibacterial agents triclosan and triclocarban formation of aggregates and higher-order complexeslnt. J. Pharm. 297 213-222. 

Nevertheless, solubilization still could be required for very insoluble molecules. Several approaches have been reported. Use of cyclodextrin as a complexation agent was shown to be effective and yielded both accelerated and pH-independent release.48 Further, in situ complexation between drug molecules and cyclodextrin in the matrix was encouraging because it would not require organic processing to render such complexation prior to matrix preparation. Recently, other approaches, such as incorporating... 

Lipids also can be beneficial for cells in culture, since some substances absorbed by the cells need to be solubilized in lipids, or in some cases the toxicity of compounds may be reduced by complexation with lipids. The absence of essential lipids such as linoleic acid, lecithin, cholesterol, ethanolamine, or phosphorylcholine can result in the decrease of cloning efficiency and in reduction in the size of colonies, as shown for insect cells by Echalier (1997). However, one of the difficulties in supplying lipids at reasonable concentrations is their low solubility. To circumvent this limitation, lipids can be emulsified with complexing agents such as Pluronic F68 or cyclodextrin (Maiorella et al., 1998). 

Okimoto, K., Rajewski, R. A., and Stella, J. V. (1999), Release of testosterone from an osmotic pump tablet utilizing (SBE)7m-B-cyclodextrin as both a solubilizing and an osmotic pump agent, /. Controlled Release, 58, 29-38. 

Ueda, H. Ou, D. Endo, T. Nagase, H. Nagai, T. Evaluation of a sulfobutyl ether p-cyclodextrin as a solubilizing/stabilizing agent for several drugs. In Symposium on Pharmaceutical Applications of Cyclodextrins Lawrence, KS, June 29-July 2, 1997. 

Solid solubilizers such as the (3-cyclodextrins act by forming soluble inclusion complexes in aqueous solution. These molecules, as with surface active agents, are amphiphilic, meaning that they contain hydrophobic... 

P-Cyclodextrin derivatives are more water-soluble than P-cyclodextrin, and studies have shown that they have greater solubilizing action with some drugs such as ibuproxam, a poorly water-soluble anti-inflammatory agent. ... 

Sulfobutylether P-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins. It can also enhance their solubility and stability in water. The first application of sulfobutylether P-cyclodextrin was in injectable preparations it can also be used in oral solid and liquid dosage forms, and ophthalmic, inhalation, and intranasal formulations. Sulfobutylether P-cyclodextrin can function as an osmotic agent and/or a solubilizer for controlled-release delivery, and has antimicrobial preservative properties when present at sufficient concentrations. 

In a subsequent work, the solubilization of this substance by pH control combined with co-solvents, surfactants, or complexing agents was investigated (Li et al. 1999). Control of the solution pH was effected in combination with various surfactants (polysorbates 20 and 80) or cyclodextrin complexing agents. It was determined that the theoretical model developed by the authors could be successfully used to characterize the effects of pH, pKa, complexation constants, micelle partition coefficients, or solubilizing power of cosolvents on the solubility of ionized and non-ionized compounds. 

After cyclodextrins and co-solvents, other approaches can be applied including the use of surfactants and micelle forming agents. Surfactants can be classified as amphoteric (lecithin), non-ionic (Tween 80 or Cremophor EF) or ionic (sodium lauryl sulfate or sodium palmitate). Cremophor is a polyoxyethylenated castor oil derivative which is a common solubilizing excipient in a number of formulations including those for paclitaxel, propofol, teniposide and clanfenur... 

Brewster ME, Hora MS, Simpkins JW, and Bodor N. Use of 2-Hydroxypropyl-Cyclodextrin as a Solubilizing and Stabilizing Agent for Protein Drugs. Pharm Res 1991 8 792-795. 

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