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The solubility of erythromycin A dihydrate in pure ethanol, propan-2-ol, methanol, acetone, chloroform, and acetone + water was measured by a synthetic method at temperature ranging from 293.20 K to 323.00 K at atmosphere pressure. The laser monitoring observation technique was used to determine the disappearance of the solid phase in a solid + liquid mixture. The results of these measurements were correlated by a semiempirical Apelblat equation.

The focus of this contribution is on the understanding of solubility that is a prerequisite to any meaningful measurement, reporting, and interpretation of solubility data. A brief reprise of the thermodynamics of solubility is followed by a summary of ‘excess solvent’ and ‘excess solid’ methods of measurement in common usage. Case studies illustrate how temperature, polymorph, water, and impurities can change the measured solubility by factors of 2 or more. The interplay between these factors and the method of measurement is explored, drawing on the differing academic, industrial, and geographical perspectives of the authors.

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The application of in situ focused beam reflectance measurement (FBRM) and particle vision measurement (PVM) in monitoring transformation of glycine polymorphs is introduced. The effect of solvent composition and temperature on the transformation from -to r-glycine was investigated. It is noted that the transformation kinetics are highly sensitive to both the solvent composition and temperature and the transformation rate is a function of ethanol content in aqueous ethanol mixtures. At 303 K, high initial ethanol concentration accounts for a steady transformation. At the same ethanol content, the transformation rate decreases with decrease in temperature. A smoother transformation was observed at 293 K. The results are consistent with the solvent-mediated transformation mechanism in which -glycine dissolves and r-glycine nucleates and grows. The thermodynamically stable γ-glycine was not observed. Understanding these effects can aid optimization and improve process control.

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The solubility of fumaric acid in propan-2-ol, ethanol, acetone, and propan-1-ol was measured by a synthetic method at temperatures ranging from (279 to 352) K at atmospheric pressure. The laser monitoring observation technique was used to determine the disappearance of the solid phase in a solid + liquid mixture. The results of these measurements were correlated by a modified Apelblat equation.

Additive is an effective factor in controlling crystallization of polymorph. l-Tryptophan, l-leucine, l-threonine, l-histidine, l-alanine, and l-valine, as additives during l-glutamic acid crystallization, were investigated for probing their effects on the polymorphic transformation. l-Tryptophan was then chosen as a representative case to evaluate the effect of addition concentration on the morphology, nucleation, and polymorphic transformation rate of l-glutamic acid. It is shown that all these additives have a certain influence on the polymorphic transformation and the presence of a bulky side chain (phenyl) in l-tryptophan and l-histidine is identified as an essential feature in achieving stabilization of the α-polymorph. When the concentration of l-tryptophan reaches above 0.008 M, the elongation of crystals occur. Increasing l-tryptophan concentration, the transformation time and nucleation rate of l-glutamic acid are retarded. The inclusion behavior of additive molecules in l-Glu crystals was investigated, and the results show that the effect of additive molecule on the polymorphic transformation may be through incorporating into crystal structures by adsorption.