Polymorph Farming of Acetaminophen and Sulfathiazole on a Chip

Abstract

Template surfaces were thought to provide specific functional groups to either change the energy barrier for the nuclei formation of the thermodynamically metastable Form I or alter the droplet contact angle and the droplet surface area which was related to the droplet evaporation time. The evaporation time determines the amount of time available for the polymorphic transformation from Form I to Form III. Apparently, droplet volumes could also determine the amount of time needed to reach supersaturation and the amount of time available for a polymorphic transformation from Form I to Form III. In addition, the molecular conformation and viscosity of solvents such as methanol might alter the original nucleation kinetics in water and lead to a more rapid polymorphic transformation from Form I to Form III. Template films of PE-Chl and chitosan were found to be critical for determining the face of a millimeter-sized acetaminophen crystal at the template-crystal interface. The idea of performing polymorph screening on the template film deposited on a chip has opened up a new doorway to examine the roles of: (1) various kinds of drug carrier in the form of a template film, (2) the droplet volume of a saturated solution, and (3) the type of solvent used, in polymorphic control. Growing millimeter-sized crystals directly on the chip of template has also provided a convenient technology enabling platform for examining the crystal-template interface by solid-state characterization techniques such as ESCA.

Hyphenated spectroscopy as a polymorph screening tool

“…The composition of the solvent, heating/cooling profiles, agitation and seeding are just few of many parameters that can affect the outcome of the crystallization. The scale of the crystallization also plays a role and therefore the solid forms successfully generated at very small scale, such as on a chip [7] or self-assembled monolayers (SAMs) [8], cannot always be produced at production scale.…”

Surface Mediated Structures: Stabilization of Metastable Polymorphs on the Example of Paracetamol

“…The controlled preparation of polymorphic structures and different crystal morphologies has become a hot topic in several research areas such as pharmaceutical technology, 1,2 crystal engineering, 3,4 organic electronics 5 as well as in material science. 6 Various polymorphs of a single substance differ by means of their physical and chemical properties such as solubility, bioavailability, morphology, crystal structure, or even thermodynamic stability.…”

Polymorphism and Solvatomorphism 2006

“…41 The effect of epitaxial surface composition was studied in detail for acetaminophen and sulfathiazole crystallized on silicon wafers or on template films. 42 For sulfathiazole, the metastable Form-I was obtained on nonannealed chitosan films, while the stable Form-III was formed on annealed films.…”