Physical properties of parabens and their mixtures: solubility in water, thermal behavior, and crystal structures.
The peculiar solubility behavior of propylparaben (propyl ester of 4-hydroxybenzoic acid) in aqueous solution, when tested separately and together with methyl-, ethyl-, and butyl-parabens, has been investigated in detail. The results clearly indicate that the decrease in solubility (approximately 50% compared to the solubility value of propylparaben alone) is typical of those mixtures containing also ethylparaben, as demonstrated by solubility experiments on binary, ternary, and quaternary mixtures of the parabens. Phase diagrams of all the six binaries show that propylparaben and ethylparaben are the only pair that form almost ideal solid solutions near the melting temperatures. Moreover, phase-solubility analysis shows that propylparaben and ethylparaben, at room temperature, can also form solid solutions whose solubility is related to the composition of the solid phase at equilibrium. To achieve an independent confirmation of the possible solid solution formation that supports the above interpretation of the solubility behavior, the crystal structures of the four parabens have been examined and isostructurality has been found to exist only between ethylparaben and propylparaben. Powder X-ray diffraction has also been performed on ethylparaben, propylparaben, and their solid solutions obtained by recrystallization from water. The progressive shift of distinctive diffraction peaks with phase composition clearly indicates that propylparaben and ethylparaben form substitutional solid solutions. The small value (<1) of the disruption index provides thermodynamic support for substitutional solid solutions based on isostructural crystals.
Giordano
F
F
Dipartimento Farmaceutico, University of Parma, Viale delle Scienze, 43100 Parma, Italy. giordano@unipr.it
Bettini
R
R
Donini
C
C
Gazzaniga
A
A
Caira
M R
MR
Zhang
G G
GG
Grant
D J
DJ
D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D006358:Hot Temperature; D010226:Parabens / Q000737:chemistry*; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
D010226:Parabens; D011310:Preservatives, Pharmaceutical; D014867:Water; C012313:ethyl-p-hydroxybenzoate; C038091:butylparaben; C015358:methylparaben; C006068:propylparaben