Cocrystal Systems of Pharmaceutical Interest: 2012-2014.

Developments in the field of pharmaceutical cocrystals have been documented in the form of chronological review articles, and the present review encompasses articles published during 2012, 2013, and 2014. Appropriate publications were drawn from the major physical, crystallographic, and pharmaceutical journals, being sorted according to the identity of the drug substance involved. This information is contained in tabular form, where the primary sorting has been by compound name and year of publication. For each entry, the table also contains the bibliographic citation to the paper, a complete list of the authors, and the title of the paper.

Mid-Infrared Spectroscopy of Pharmaceutical Solids.

It is now well established that infrared absorption spectroscopy is a powerful technique for the physical characterization of pharmaceutical solids. Besides being a preferred methodology for identification purposes, one can use trends in the energy values in the spectra as a means to study the solid-state properties of the system. FTIR spectra are often used to evaluate the type of polymorphism existing in a drug substance, can be very useful in studies of the water contained within a hydrate species, and are emerging as a technique of choice for the study of cocrystal systems. In this review, an overview of the theoretical foundations for infrared spectroscopy will be presented, which will be supported by illustrations as to how the methodology can be used.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as a Forensic Method to Determine the Composition of Inks Used to Print the United States One-cent Blue Benjamin Franklin Postage Stamps of the 19th Century.

Through the combined use of infrared (IR) absorption spectroscopy and attenuated total reflectance (ATR) sampling, the composition of inks used to print the many different types of one-cent Benjamin Franklin stamps of the 19th century has been established. This information permits a historical evaluation of the formulations used at various times, and also facilitates the differentiation of the various stamps from each other. In two instances, the ink composition permits the unambiguous identification of stamps whose appearance is identical, and which (until now) have only been differentiated through estimates of the degree of hardness or softness of the stamp paper, or through the presence or absence of a watermark in the paper. In these instances, the use of ATR Fourier transform infrared spectroscopy (FT-IR) spectroscopy effectively renders irrelevant two 100-year-old practices of stamp identification. Furthermore, since the use of ATR sampling makes it possible to obtain the spectrum of a stamp still attached to its cover, it is no longer necessary to identify these blue Franklin stamps using their cancellation dates.

Butyl methoxy dibenzoylmethane.

A comprehensive profile on Butyl methoxy dibenzoylmethane, one of the most commonly used ultraviolet (UV) filters in topical sunscreen products, is prepared. This UV filter, often referred to as Avobenzone, has its main absorbance in the UVA I region of the spectrum and is susceptible to photodegradation. The profile contains the following sections: general information, use and mechanism of action, method of preparation, physical characteristics, methods of analysis, stability, and toxicity. The physical characteristics section includes the melting range, differential scanning calorimetry, partition coefficient, ionization constant, solubility, and UV, infrared, nuclear magnetic resonance ((1)H NMR and (13)C NMR) and mass spectrometry and X-ray powder diffractometry. The method of analysis section in addition to compendial identification and purity and assay methods includes thin-layer gas and high-performance liquid chromatography. The photostability and photostabilization of Butyl methoxy dibenzoylmethane, in addition to its toxicity, are also documented.

Paroxetine hydrochloride: polymorphs and solvatomorphs.

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 paroxetine hydrochloride have 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 paroxetine hydrochloride has been crystallized in four genuine nonsolvated polymorphic forms and in four fully characterized solvatomorphic forms.

Stereoselectivity in the salt-cocrystal products formed by phenylglycinol or phenylglycine with their respective sodium or hydrochloride salts.

The salt and stereoselective cocrystal phenomena associated with 2-phenylglycinol and 2-phenylglycine have been studied using X-ray powder diffraction and differential scanning calorimetry. The chiral identities of the free acids and their sodium salts, or the free bases and their chloride salts, were found to play a determining role as to whether a salt-cocrystal product could or could not be formed. In particular, when cocrystallization of an enantiomerically pure basic or zwitterionic substance with its enantiomerically pure acid addition salt was attempted, a salt-cocrystal was only obtained when the absolute configuration of the two reactants is opposite. On the other hand, it has been found that no stereoselectivity in salt-cocrystal formation existed in the cocrystallization of an enantiomerically pure acidic or zwitterionic substance with its enantiomerically pure base addition salt.

Pharmaceutical cocrystals: the coming wave of new drug substances.

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.

Polymorphism and solvatomorphism 2010.

Papers and patents that deal with polymorphism (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 solvatomorphism (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) have been summarized in an annual review. The works cited in this review were published during 2010 and were drawn from the major physical, crystallographic, and pharmaceutical journals. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and US patents issued during 2010.

Polymorphism and solvatomorphism 2009.

Research papers and issued patents involving polymorphism (i.e., crystal systems for which a substance can exist in structures characterized by different unit cells, but in which each of the forms has exactly the same elemental composition) and solvatomorphism (i.e., systems in which the crystal structures of the substance are defined by different unit cells, but wherein these unit cells differ in their elemental composition through the inclusion of one or more molecules of solvent) have been summarized in an annual review. The works cited in this review were published during 2009, and were sourced from the major physical, crystallographic, and pharmaceutical journals. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization, properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and US patents issued during 2009.

Direct crystallization of enantiomers and dissociable diastereomers.

Molecules whose mirror images cannot be superimposed on each other are identified as being chiral, and a very important branch of separation science has developed around the resolution of compounds having pharmaceutical interest. At one time, scientists associated the phenomenon of optical rotation with the presence of carbon atoms bound to four different molecular fragments, and these asymmetrically substituted carbon atoms became known as "asymmetric carbons." Continued work showed that compounds incapable of rotating the plane of polarized light, but which were known to contain at least one asymmetric carbon atom, could be separated into chemically identical "optical isomers" that now exhibited the phenomenon of optical rotation. Over time, it became clear that optical activity could exist in compounds having no asymmetric atoms, and that other compounds existed that contained two or more asymmetric carbons, but still could not be rendered optically active. These findings necessitated a return to the proposal of Pasteur, who held that optical activity is a consequence of molecular dissymmetry. In other words, a molecule superimposable with its mirror image cannot be optically active, and any molecule not superimposable with its mirror image will exhibit optical activity.

Cocrystal systems of pharmaceutical interest: 2009.

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.

Polymorphism and solvatomorphism 2008.

Papers and patents that deal with polymorphism and solvatomorphism have been summarized in an annual review. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and United States patents issued during 2008.