(653g) Solubilty of Acetylsalicylic Acid in Some Organic Solvents

The drug known as aspirin is an ordinary medicine that is easily found at any drugstores around the world. Little more than a hundred years ago it was considered to be a miraculous drug that had just appeared at drugstores and pharmacies around Europe. Several similar components had already been produced, though none of them would ever be as successful as the component that is the active principle of aspirin, i.e., the acetylsalicylic acid.

Currently there have been countless reports on the benefits of a small dose of aspirin for the secondary prophylaxis of manifold cardiovascular diseases, such as brain stroke and myocardial infarction due to its capacity to inhibit the thromboxane synthesis, which prevents the formation of both brain and heart thrombi. It is also increasingly evident that aspirin, when regularly used, might play an important role in the prevention of colorectal cancer. Such hypothesis was the topic of an evaluation presented by a working team at the International Agency for Cancer Research in Lyon, France.

Especially in regard to solubility, a few researchers are exclusively concerned with obtaining values for a unique temperature without assessing the solubility in relation to temperature. The solubility is an important parameter to be determined because a series of processes depend upon its recognition as in the event of crystallization. Its study initially faces the problem of lack of information about the behavior of this substance in solution.

The behavior of the acetylsalicylic acid solubility in different temperatures affects, among other aspects, the choice of a crystallization, purification, and storage process. The solubility ? or saturation condition ? is experimentally determined by heating the suspension and observing at which temperature the entire solid melts. Above this temperature, the solution is said to be sub-saturated, i.e., the entire solute remains dissolved. However, it is possible to cool the same solution at temperatures below the saturation temperature without leading to crystallization. In this case, the solution is known as over-saturated.

Thus, for the determination of acetylsalicylic acid solubility curves and aiming at minimizing the effects of the metastable zones, which could hide the real acetylsalicylic acid solubility, the polythermic method proposed by Nývlt and Giulietti was used.

The temperature dependence of solubility in pure solvents, considering the system as ideal, can be described by a general solubility equation as follows

Where R is the gas constant, T_f is the fusion temperature, T is the study temperature, Δc_p corresponds to the thermal capacity variation between the liquid and the solid phases, Δh^f is the fusion enthalpy,  x is the molar fraction ? or solubility ? and the index 1 stands for the solute. So we can calculate the ideal solubility in any desired temperature range.

In the model proposed by Nývlt and Giulietti, the author considered a binary system where component 1 does not form solid solutions with the solvent.  The equilibrium thermodynamic condition at constant pressure is the equality of chemical potentials, µ, of the components in both phases.

Based on this consideration, the authors elaborated an expression that establishes a straight relation between the solubility of a given substance and the system temperature so that the activity coefficient would not explicitly appear in the equation, although it is contained within the adjustable parameters N₁, N₂, N₃

Therefore, this study is aimed at contributing towards the determination of solubility of acetylsalicylic acid in four organic solvents, i.e., ethanol, acetone, propylene glycol, and 2-propanol, in different temperatures, in addition to comparing their solubility values with the expected from an ideal solution. The experimental solubility data were correlated with Nývlt model.

In addition to the industrial relevance, the choice of the solvents was undertaken by taken into account the temperature range in order to obtain an enhanced distribution of temperatures for the solubility study.

It has been noted that the solubility of acetylsalicylic acid is highest in acetone to all studied temperature range until T(K) = 326.3. Propylene glycol presents lower solubility data to all studied temperature range. The solvent, who presents the lowest average percent logarithmic deviation, concerning the ideality of the system, was the ethanol, and the highest value of average percent logarithmic deviation was found in propylene glycol solutions. The experimental solubility data were correlated with Nývlt solubility model. We conclude that Nývlt model was capable to represent properly the experimental data.