Dissolution solubility parameters

Tseng et al. [164] suecessfully used UNIFAC to optimize polymer-solvent interactions in three-solvent systems, determining polymer activity as a function of the solvent eomposition. The composition yielding the minimum in polymer aetivity was taken as the eriterion for optimum interaetion, and it eompared well with experimental measurements of dissolution rate and solution clarity. Better agreement was obtained using UNIFAC than using solubility parameter methods. 

Thus, %F is defined as the area under the curve normalized for administered dose. Blood drug concentration is affected by the dynamics of dissolution, solubility, absorption, metabolism, distribution, and elimination. In addition to %F, other pharmacokinetic parameters are derived from the drug concentration versus time plots. These include the terms to describe the compound s absorption, distribution, metabolism and excretion, but they are dependent to some degree on the route of administration of the drug. For instance, if the drug is administered by the intravenous route it will undergo rapid distribution into the tissues, including those tissues that are responsible for its elimination. 

One approach to the study of solubility is to evaluate the time dependence of the solubilization process, such as is conducted in the dissolution testing of dosage forms [70], In this work, the amount of drug substance that becomes dissolved per unit time under standard conditions is followed. Within the accepted model for pharmaceutical dissolution, the rate-limiting step is the transport of solute away from the interfacial layer at the dissolving solid into the bulk solution. To measure the intrinsic dissolution rate of a drug, the compound is normally compressed into a special die to a condition of zero porosity. The system is immersed into the solvent reservoir, and the concentration monitored as a function of time. Use of this procedure yields a dissolution rate parameter that is intrinsic to the compound under study and that is considered an important parameter in the preformulation process. A critical evaluation of the intrinsic dissolution methodology and interpretation is available [71]. 

Polymeric materials are susceptible to solution by solvents or liquids when the solubility parameters (see Secs. 8.1 and 8.2) of the polymer and solvent or liquid are similar. Insertion of mild cross-linking discourages dissolution and is often employed to prevent dissolution of polymeric materials,... 

An alternative approach is to measure the minimum temperature required to bring about dissolution of the polymer, again in a series of solvents of known solubility parameters. This is illustrated in Figure 2.25. The solubility parameter of the polymer is taken to be the value of Si that corresponds to the smallest required increase in temperature. 

Figure 2.25 The dissolution temperature method for determining polymer solubility parameters. Reprinted with permission from J. E. Mark, Physical Chemistry of Polymers, ACS Audio Course C-89, American Chemical Society, Washington, DC, 1986. Copyright 1986, American Chemical Society.

We can conclude that two substances with equal solubility parameters should be mutually soluble due to the negative entropy factor. This is in accordance with the general rule that chemical and structural similarity favours solubility. As the difference between 81 and S2 increases, the tendency towards dissolution decreases. 

A thermodynamic method, more fitting to this chapter, has been proposed by Nauman et al. They claim a process for the separation of a physically mixed solid polymers by selective dissolution. They rely on the different polymer solubility characteristics. Tables of this property have been reported and are based on regular solution theory and Hildebrand solubility parameters. The core of the Nauman invention is to find suitable solvents to dissolve particular polymers under defined temperature and pressure conditions. A mixture of polymers is first added to one solvent, at a given temperature, in order to dissolve a particular polymer. The remaining polymer mixture is then treated at a higher temperature with the same solvent or with a different solvent. For clarity, two examples are taken from the patent."... 

Solubility parameter data (Table 3) provide less clear-cut differences between the good and poor solvents in Table 7. Mention was made of the need for 8, 8rf, 8p, and 8/, parameters for solvent and solute to be similar for dissolution to take place. There are no measured solubility parameter data available for humic substances, and so accurate predictions cannot be made based on parameter values for solutes and solvents. 

When determining the mutual solubility of substances by -values one should remember that in the absence of strong specific intermolecular interactions, thermodynamic miscibility between the substances mixed (complete mutual dissolution among them) has been detected if their solubility parameters differed by no more than 2 (42). 

For liquids of low molecular weight the energy necessary to separate molecules from one another is evaluated from the heat of evaporation or from the dependence of vapor pressure on temperature. Since polymers cannot be evaporated, the cohesive energy density is estimated indirectly by dissolution in liquids of known cohesive energy density. To do this, we employ the relation between the cohesive energy density and solubility parameter (Equation 3.11). 

Various organic solvents were used as reactionary medium at nonequilibrium polycondensation in solution realization [96]. The solvent type influence on the synthesis reaction main characteristics (conversion degree Q and molecular weight MM) is well known and is explained usually by solvent various characteristics (dielectric constant, solubility parameter, heat of dissolution and so on) [96]. However, up to now the indicated effects general theoretical explanation is not obtained. Besides, at the solvent type influence analysis its correlation with polycondensation process quantitative characteristics (the same Q and MM) is usually considered, but any changes of polymer structure or reaction mechanism are not assumed, although the possibility of side reactions is noted repeatedly [96]. The authors [71, 127] studied the solvent influence on the enumerated above characteristics on die example of the rules of chloranhydride of terephthalic acid and phenolfthaleine low-temperature polycondensation (polyarylate F-2), performed in 8 different solvents [128]. 

The authors [97] proposed the Eq. (82) for the dimension 8 evaluation with using the solvent 8 and polymer 8 solubility parameters. The calculation according to this equation has shown that for star-like PS-Cg 8 value changes from 9.78 (cal/cm ) fgj- usual PS in tetrahydrofuran solution up to 30.7 (cal/cm ) 2 for star-like PS-C with 22 beams in chloroform solution. It is obvious, that the effective 8 value characterizes polymer dissolution complication at dimension Z) growth or macromolecular coils densification. In Fig. 106 the dependence 8 (e) is adduced, from which the... 

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