Solubility, drugs

The majority of pharmaceutical agents do not have sufficient solubility in water and the conventional formulation system for insoluble drugs involves a combination of surfactants, organic solvents and extreme pH and temperature conditions. The combination generally generates irritation and other adverse reactions. CDs are not irritant and offer distinct advantages to solubilize various biomedical peptides and proteins, including interleukin-2, hormones, aspartame, tumor necrosis factor, /3-amyloid peptide and albumin [44]. For instance, the solubility 

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An analysis of partition coefficient data and drug solubilities in PCL and silicone rubber has been used to show how the relative permeabilities in PCL vary with the lipophilicity of the drug (58,59). The permeabilities of copolymers of e-caprolactone and dl-lactic acid have also been measured and found to be relatively invariant for compositions up to 50% lactic acid (67). The permeability then decreases rapidly to that of the homopolymer of dl-lactic acid, which is 10 times smaller than the value of PCL. These results have been discussed in terms of the polymer morphologies. 

K., The correlation of polymer-water and octanol-water coefficients Estimation of drug solubilities in polymers, Int. J. Pharm., 45, 1-11, 1988. 

Bevan, C. D., Uoyd, R. S. A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates. Anal. Chem. 2000, 72,1781-1787. 

Bergstrom, C. A. S. Computational models to predict aqueous drug solubility, permeability and intestinal absorption. Exp. Opin. Drug Metab. Toxicol. 2005, 1, 513-527. 

Bergstrom, C. A. S. D., Norinder, U., Luthman, K., Artursson, P. Experimental and computational screening models for prediction of aqueous drug solubility. Pharm. Res. 2002, 19,182-188. 

This chapter is written for a medicinal chemistry audience. The focus is on the importance of drug solubility in water and in dimethylsulfoxide (DMSO) in the types of activities likely to be of interest to medicinal chemists. The emphasis is on the discovery stage as opposed to the development stage. The reader will find numerous generalizations and rules of thumb relating to solubility in a drug discovery setting. 

Successful drugs with solubilities lower than 10 or lO molL, or in logarithmic units log Sw below -5 or -6, are rarely found, and so this may be viewed as a lower bound for promising drug candidates. On the other hand, almost all drugs have solubilities lower than O.lmolL", i.e. log Sw<-1. Thus, the range of -6[Pg.284]

It is not only the solid state of a drug that suffers from ambiguities, but also the aqueous state. The state relevant for the intrinsic solubility is the state of the saturated solution of the neutral species. Since most aqueous drug solubilities are small, direct interactions of the drug molecules are usually rare. Hence, this state is usually very similar to the state of the drug at infinite dilution in water. Most computational methods disregard saturation effects. Usually this is a good approximation, but one should keep in mind that this approximation may result in some moderate, but systematic errors at the upper end of the solubility scale. 

I J 7 Challenge of Drug SolubilitY Prediction and as H-bond interactions ... 

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