p-Aminobenzoic acid (PABA) crystallizes in two different polymorphic forms: the R-polymorph, which is the commercially available form and appears as long, fibrous needles, and the β-polymorph, which appears in the form of prisms. The thermodynamic stability and crystallization from different solvents have been studied experimentally. The system is found to be enantiotropic with a transition temperature of 25 °C, below which the β-form is the stable polymorph. The compound has been crystallized from 13 different solvents, either by slow cooling after which the product is allowed to mature in suspension, or by rapid cooling followed by immediate isolation. Needles were obtained from all solvents by both methods. In water and in ethyl acetate, at slow cooling below 20 °C, the prismatic β-form is obtained, however, often together with the needles. The β-form crystals usually needed hours or days to grow at the very slow cooling used, while needles usually appeared in seconds. By careful control of supersaturation and temperature, cooling crystallization can be performed to produce the pure β-form in water and in ethyl acetate. The influence of the solvent is explained by analysis of the crystal structures versus the possible interaction of the solvent molecules with the solute in solution. The R-form structure is governed by carboxylic acid dimers and is kinetically favored since it is believed that the corresponding dimers easily form in the solution, especially in less polar solvents.

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Predictions of solubility of nine different solid organic fine chemical compounds in water and organic solvents of relevance to industrial processing are examined. UNIFAC interaction parameters are taken from standard reference literature, extracted from liquid-vapor equilibria. For most systems, predicted solubilities deviate more than 15% from experimental values. Deviations are due to uncertainties in the estimation of the activity of the pure solid as well as to deficiencies in the estimation of activity coefficients in the solution. By comparison with results from ab initio quantum chemical calculations of the elecrostatic potential on the molecular surface of the solutes, it can be shown that a key assumption of the UNIFAC approach is not necessarily fulfilled. The properties of a functional group may depend significantly on the properties of the rest of the molecule.

The solubility of phenyl acetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid, and ibuprofen in water and in a range of organic solvents of relevance to industrial processing is reported. The solvents used are water, methanol, ethanol, 2-propanol, acetone, 4-methyl-2-pentanone, ethyl acetate, chloroform, and toluene. Solubility data are discussed from the standpoint of molecular aspects of solute-solvent interactions and by estimated solid-phase activity.

p-Aminobenzoic acid crystallizes in two different polymorphic forms:  the α-form and the β-form. The α-form crystals are needle-shaped, while the β-form crystals have a more favorable prismatic shape. The system is enantiotropic with the transition temperature at approximately 25 °C. Below the transition temperature, the β-form is the thermodynamically stable polymorph but can only be produced at very slow supersaturation generation either in water or in ethyl acetate. In the present work, the influence of ultrasound on the nucleation of p-aminobenzoic acid polymorphs has been investigated by use of several different sonication intensities and schemes. It is shown that sonication significantly reduces the induction time for nucleation. By using controlled sonication, we were able to more reproducibly crystallize the β-form at more reasonable cooling rates. In addition, sonication is found to quite selectively favor the appearance of the β-polymorph. It is even possible to produce the pure β-form above the transition temperature where it is the metastable form and impossible to produce without sonication. The α-form structure is based on centro symmetric dimers formed by the association of carboxylic acid groups, while the β-form contains four-membered hydrogen-bonded rings of alternating amino and carboxylic acid groups. It is suggested that ultrasound disturbs the building up of the dimers in the solution and thus favors the crystallization of the β-polymorph.