The preparation of typically thermodynamically unstable polymorphic structures is a challenge. However, solid surfaces are well established aids for the formation and stabilization of polymorphic structures within, for instance, organic electronics. In this study, we report the stabilization of a pharmaceutically relevant substance via a solid surface at ambient conditions. Form III of paracetamol, which is typically unstable in the bulk at standard conditions, can be stabilized with a model silica surface by a standard spin coating procedure followed by rapid heat treatment. Such a preparation technique allows the use of atomic force microscopy and grazing incidence X-ray diffraction measurements revealing detailed information on the morphology and structure of the polymorph. Furthermore, the results exhibit that this polymorph is stable over a long period of time revealing surface mediated stabilization. These findings demonstrate a novel approach to provide thermodynamic stability when applied to similar molecules with specific applications.

Polymorphism and morphology can represent key factors tremendously limiting the bioavailability of active pharmaceutical ingredients (API), in particular, due to solubility issues. Within this work, the generation of a yet unknown surface-induced polymorph (SIP) of the model drug, 5,5-diphenylimidazolidin-2,4-dion (phenytoin), is demonstrated in thin films through altering the crystallization kinetics and the solvent type. Atomic force microscopy points toward the presence of large single-crystalline domains of the SIP, which is in contrast to samples comprising solely the bulk phase, where extended dendritic phenytoin networks are observed. Grazing incidence X-ray diffraction reveals unit cell dimensions of the SIP significantly different from those of the known bulk crystal structure of phenytoin. Moreover, the aqueous dissolution performance of the new polymorph is benchmarked against a pure bulk phase reference sample. Our results demonstrate that the SIP exhibits markedly advantageous drug release performance in terms of dissolution time. These findings suggest that thin-film growth of pharmaceutical systems in general should be explored, where poor aqueous dissolution represents a key limiting factor in pharmaceutical applications, and illustrate the experimental pathway for determining the physical properties of a pharmaceutically relevant SIP.

The usage of amorphous solids in practical applications, such as in medication, is commonly limited by the poor long-term stability of this state, because unwanted crystalline transitions occur. In this study, three different polymeric coatings are investigated for their ability to stabilize amorphous films of the model drug clotrimazole and to protect against thermally induced transitions. For this, drop cast films of clotrimazole are encapsulated by initiated chemical vapor deposition (iCVD), using perfluorodecyl acrylate (PFDA), hydroxyethyl methacrylate (HEMA), and methacrylic acid (MAA). The iCVD technique operates under solvent-free conditions at low temperatures, thus leaving the solid state of the encapsulated layer unaffected. Optical microscopy and X-ray diffraction data reveal that at ambient conditions of about 22 °C, any of these iCVD layers extends the lifetime of the amorphous state significantly. At higher temperatures (50 or 70 °C), the p-PFDA coating is unable to provide protection, while the p-HEMA and p-MAA strongly reduce the crystallization rate. Furthermore, p-HEMA and p-MAA selectively facilitate a preferential alignment of clotrimazole and, interestingly, even suppress crystallization upon a temporary, rapid temperature increase (3 °C/min, up to 150 °C). The results of this study demonstrate how a polymeric coating, synthesized directly on top of an amorphous phase, can act as a stabilizing agent against crystalline transitions, which makes this approach interesting for a variety of applications.

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The supramolecular rearrangements of biopolymers have remained difficult to discern. Here, we present a versatile approach that allows for an in situ investigation of two major types of rearrangements typically observed with cellulose, the most abundant biopolymer on earth. Model thin films were employed to study time-resolved pore size changes using in situ grazing incidence small-angle X-ray scattering (GISAXS) during regeneration and drying.