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Milford, NJ, United States

The chloride salts formed by benzylamine and α-methylbenzylamine have been characterized using X-ray powder diffraction, differential scanning calorimetry, and infrared absorption spectroscopy. In addition, X-ray powder diffraction and differential scanning calorimetry have been used to establish formation or lack of formation of the 1:1 stoichiometric salt-cocrystal products containing the chloride salts and their respective free bases. For α-methylbenzylamine (which contains a single dissymmetric center), the chiral identities of the free bases and chloride salts were found to play a determining role as to whether a salt-cocrystal product could or could not be formed. It was found that a salt-cocrystal product could only be formed if the salt and free base were of opposite absolute configurations. For those systems where the existence of cocrystals was demonstrated, assignments were derived for the observed peaks in the infrared absorption spectra of the reactants and their products. © 2011 American Chemical Society.

Brittain H.G.,Center for Pharmaceutical Physics
Profiles of Drug Substances, Excipients and Related Methodology | Year: 2012

The polymorphic (crystal systems for which a substance can exist in structures defined by different unit cells, and where each of the forms has the same elemental composition) and solvatomorphic (systems where the crystal structures of the substance are defined by different unit cells, but where these unit cells differ in their elemental composition through the inclusion of one or molecules of solvent) landscape of aripiprazole has been critically evaluated in order to learn how many authentic crystal forms have actually been discovered. After a survey of the patent and open literature, it was determined that aripiprazole has been crystallized in nine genuine polymorphic forms and in eight genuine solvatomorphic forms. It was also learned that several other reported "crystal forms" did not consist of a single solid-state phase, and were most likely mixtures of different structures. © 2012 Elsevier Inc.

Brittain H.G.,Center for Pharmaceutical Physics
Journal of Pharmaceutical Sciences | Year: 2013

Solid crystalline phases containing two cocrystallized components offer a new development pathway whereby one can potentially improve the physical characteristics (i.e., equilibrium solubility, dissolution rate, solid-state stability, etc.) of a drug substance that exhibits a profile that is less than desirable. In this commentary, the topic of pharmaceutical cocrystals will be briefly explored, and a short exposition of the solubility and dissolution rate advantages that have been realized in various systems will be provided. The Guidance for Industry document recently proposed by United States Food and Drug Administration will be outlined, and its requirements explained. Finally, the subset of pharmaceutical cocrystals that consist of a drug substance and a salt of that substance (termed a salt cocrystal) will be examined to illustrate this additional class of pharmaceutical cocrystals that may offer significant scientific and regulatory advantages. © 2012 Wiley Periodicals, Inc.

X-ray powder diffraction, differential scanning calorimetry, infrared absorption spectroscopy, and Raman spectroscopy have been used to study the phenomenon of salt formation in four benzenecarboxylic acids (benzoic acid, phenylacetic acid, hydrocinnamic acid, and 4-phenylbutanoic acid), and in the 1:1 stoichiometric products formed by the cocrystallization of a free acid and a sodium salt. Assignments were derived for the observed peaks in both infrared absorption and Raman spectra of the reactants and their products. In all instances, it was observed that the energy of the antisymmetric stretching mode of the carbonyl group of the free benzenecarboxylic acid invariably shifted to higher energies when that acid formed a cocrystal with a sodium salt of another benzenecarboxylic acid. In addition, the symmetric stretching mode of the benzenecarboxylic acid carbonyl group disappeared in the Raman spectrum of its sodium salt and was also absent in the Raman spectrum of the cocrystal product. It was also found that the antisymmetric carboxylate anion stretching mode, the symmetric carboxylate anion stretching mode, the out-of-plane carboxylate deformation mode, and the vibrational modes associated with the phenyl ring and alkane side chains were not useful spectroscopic tools to differentiate cocrystal and sodium salt, as the observed differences of these vibrational modes did not exhibit significantly consistent differences between the various forms. © 2010 American Chemical Society.

Brittain H.G.,Center for Pharmaceutical Physics
Profiles of Drug Substances, Excipients and Related Methodology | Year: 2011

As scientists become more aware of a substantial expansion in the scope of solid-state structural variations that can be obtained through the cocrystallization of several molecules in a single lattice structure, studies of the mixed molecular crystal systems known as cocrystals have mushroomed. Along these lines, workers have researched the assembly of supramolecular synthons and crystal engineering in ever-increasing efforts to produce materials having new and useful properties.For the purposes of this review, cocrystal systems will be regarded as those mixed crystal systems where the individual components exist as solids under ambient conditions. Particularly useful guidance has been provided by Aakeröy, where cocrystal formation from supramolecular synthons is to be considered as forming from discrete neutral molecular species that are solids at ambient temperatures, and where the cocrystal is a structurally homogeneous crystalline material that contains the building blocks in definite stoichiometric amounts. © 2011 Elsevier Inc.

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