Solubilization of drugs

Solutions of cresol with soap were early pharmaceutical examples of solubilized systems. Phenol itself is soluble in water to the extent of 7.7 % (w/v), but it has disadvantages the alternatives, cresol, chlorocresol, chloroxylenol, and thymol, are much less soluble in water, and their use as disinfectants has led to the need for formulation in surfactant solutions. 

Solutions of phenols in ionic systems exhibit similar behaviour. An initial fall in the solubility of 2-hydroxyphenol and 4-benzylphenol in potassium laurate solutions was noted below the CMC of the soap [17]. Few workers have commented on this insolubilization compounds with very low water solubility possibly do not show this property. That it is not restricted to phenols is shown by the results of Heller and Klevens [18] for ethyl benzene in potassium laurate. Ethyl benzene has a solubility in water similar to that of 4-benzylphenol. 

The binding of series of phenols, cresols and xylenols to the non-ionic surfactant cetomacrogol 1000 can be described by a Langmuir adsorption isotherm [19] 

Values of Pq in 0.1 m NaCl are also shown for a few compounds in this Table. A log-log plot of binding capacity and aqueous solubility yields a straight line. Azaz 

Compound (moll X 10 ) Pq in water NaCI (moir X 10 ) NaCl  

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Techniques of Solubilization of Drugs, edited by Samuel H. Yalkowsky Orphan Drugs, edited by Fred E. Karch... 

The number of studies describing the solubilization of drug compounds by cyclodextrins is extraordinarily large, and the recent state of the field has been summarized [64,65]. 

S. H. Yalkowsky, Techniques of Solubilization of Drugs, Marcel Dekker, New York, 1981. 

A. T. Florence, Drug Solubilization in Surfactant Systems, in Techniques of Solubilization of Drugs (S. H. Yalkowsky, ed.), Marcel Dekker, New York, 1981, pp. 15-89. 

Yalkowsky, S.H. and Roseman, T.J. (1981). Solubilization of drugs by cosol fedlspiques of Solubilization of Drugs, Yalkowsky, S.H. ed., Marcel Dekker, Inc. 

Repta, A. J. 1981. Alteration of apparent solubility through complexatiorfeblnniques of Solubilization of Drugs. Edited by S. FI. Yalkowsky, New York Marcel Dekker, Inc. 

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. 

The solubilization of drugs can be treated in terms of an association equilibrium between the solutes and the micelles in a micellar solution. Thus,... 

Amidon, G.L. 1981. Drug derivatization as a means of solubilization Physicochemical and biochemical strategies. In Techniques of solubilization of drugs, ed. S.H. Yalkowsky, 183. New York Marcel Dekker. 

An area where CDs have a significant therapeutic benefit is in the solubilization of drugs intended for ophthalmic use. Corneal permeability favors moderately lipophilic drugs. These compounds often have a low aqueous solubility. Thus, the CDs are being extensively exploited for their usefulness in increasing the solubility of insoluble and poorly soluble drugs and keeping them at the corneal barrier. 

Ionic derivatives of cydodextrins have also been made. These derivatives exhibit high solubility in aqueous systems. Complexes made with ionic derivatives are also very soluble. A sulfated derivative has been found to be useful for solubilization of drugs. It also has been found to mimic heparin and act as an inhibitor of infection of cells by viruses. A sulfobutyl ether derivative is also capable of solubilizing various drugs.67,68... 

Distribution and Solubilization of Drug Chemicals by Inclusion Complex Formation... 

Solubilization of Drugs in Aqueous Media, p. 3311. Tablet Formulation, p. 3641. 

Elorence, A.T. Drug solubilization in surfactant systems. In Techniques of Solubilization of Drugs Yalkowsky, S.H., Ed. Marcel Dekker, Inc. New York, 1981 15-89. 

Several methods for effective solubilization of drugs into polymer micelles have been developed (Fig. 2). The dialysis method (Fig. 2A) is most widely used for many polymeric micelle systems. The first step involves the dissolution of both polymer and drug in a water-miscible organic solvent such as acetonitrile, acetone, dimethylformamide, or ethanol. Then, the polymer-drug solution is dialyzed against water. As the organic... 

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