Factors Influencing Solubility

In order to develop a proper QSPR model for solubility prediction, the first task is to select appropriate input deseriptors that are highly correlated with solubility. Clearly, many factors influence solubility - to name but a few, the si2e of a molecule, the polarity of the molecule, and the ability of molecules to participate in hydrogen honding. For a large diverse data set, some indicators for describing the differences in the molecules are also important. 

In addition to cost, several factors influence the choice of salt for a particular appHcation. The ammonium salt is the most soluble in water, but for some apphcations the presence of the ammonium ion maybe undesirable. The sodium salt is almost as soluble as the ammonium salt at ambient temperatures and above. The potassium salt is much less soluble. 

One important factor influencing the solubility of rosin derivatives is its tendency to crystallize. Initially, a rosin product may appear to be soluble in a given solvent, but on standing, the rosin will crystallize out of soluble solution. This tendency of rosin to ciystallize can be overcome by derivatization, mainly esterification. 

The factors influencing the corrosion of metals in soil are more numerous than those prevailing in air or water, and the electrochemical effects are more pronounced. Moreover, soils vary widely in their composition and behaviour even over very short distances. It is difficult therefore to obtain reliable data. It is evident, however, that zinc has considerable resistance to corrosion when buried, and the greatest attack is caused by soils which are acid or contain large amounts of soluble salts. 

Investigation of the differences in crystal packing between (431) and (426) from comparison of their respective X-ray structures, revealed that (431) was more tightly packed than (442), reflected in their respective melting points of 235 and 170 °C. It was postulated that the absence of in vivo activity for (431) may be explained by the resultant reduction in water solubility and dissolution rate compared with (426). The comparatively high calculated polar surface area of (431) (122.5A ) compared with (426) (89.3 A ) was also proposed as a factor influencing the marked difference in bioavailability between the two related compounds. Compound (426) (SLV-319) is currently being developed with Bristol-Myers Squibb for the potential treatment of obesity and other metabolic disorders. Phase I trials for obesity were started in April 2004. Earlier Phase I clinical trials for the treatment of schizophrenia and psychosis, which commenced in April 2002, appear to have been abandoned. 

McFarland, J. W. Du, C. M. Avdeef, A., Factors influencing the water solubility of crystalline drugs, in van de Waterbeemd, H. Lennemas, H. Artursson, P. (eds.), Drug Bioavailability. Estimation of Solubility, Permeability, Absorption and Bioavailability, Wiley-VCH, Weinheim, 2003 (in press). 

Factors Influencing the Water Solubilities of Crystalline Drugs... 

Acyl migration is a reversible process, and external factors (for example, solubility) can influence the equilibrium. Thus, after dissolution of methyl 2-0-benzoyl-4,6-0-benzylidene-a-D-glucopyranoside in acetone-aqueous sodium hydroxide, almost immediate crystallization of the 3-benzoate occurred, in 65% yield.549 Similarly, benzyl 3-0-benzoyl-4,6-0-benzylidene-/3-D-galactopyranoside yielded the 2-... 

Particles may be trapped on the biofilm surface or in voids of the biofilm where any organics may be hydrolyzed and further take part in the transformation processes. A number of factors influence adsorption and desorption of particles, such as particle size, surface charge, pH, etc., as well as biofilm surface properties and bulk water flow pattern. Studies of model biofilms have shown that water flows into the biofilm in small channels, making the prediction of transport of particles as well as soluble compounds complex (Norsker et al., 1995). 

Hydrodynamics in the upper GI tract contribute to in vivo dissolution. Our ability to forecast dissolution of poorly soluble drugs in vitro depends on our knowledge of and ability to control hydrodynamics as well as other factors influencing dissolution. Provided suitable conditions (apparatus, hydrodynamics, media) are chosen for the dissolution test, it seems possible to predict dissolution limitations to the oral absorption of drugs and to reflect variations in hydrodynamic conditions in the upper GI tract. The fluid volume available for dissolution in the gut lumen, the contact time of the dissolved compound with the absorptive sites, and particle size have been identified as the main hydrodynamic determinants for the absorption of poorly soluble drugs in vivo. The influence of these factors is usually more pronounced than that of the motility pattern or the GI flow rates per se. 

Since solubility and permeability are the two most important factors influencing oral absorption of drugs, the following biopharmaceutical classification system (BCS) for drug substances, based on the work by Amidon et al.,67 has been recommended by the FDA 68... 

The solubilities of 5b at 323 K and various pressures are shown in Fig. 13. Dissolved 5b is not detected below 10 MPa. It is obvious that for these metal complexes having a negligible vapor pressure, the density of SCCO2 is the most important factor influencing the solubility. For 5b, at 23.7 MPa, the solubility amounts to 16.7 mmolcm". Compared to the solubilities of different substituted phosphines in SCCO2 published earlier, lower solubilities of the corresponding complexes are expected in general [56,122,135]. 

Other factors influencing solubility and the solubility product... 

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