Liquid crystals (LCs) are known to undergo rapid ordering transitions with virtually no hysteresis. We report a remarkable counterexample, itraconazole, where the nematic to smectic transition is avoided at a cooling rate exceeding 20  K/s. The smectic order trapped in a glass is the order reached by the equilibrium liquid before the kinetic arrest of the end-over-end molecular rotation. This is attributed to the fact that smectic ordering requires orientational ordering and suggests a general condition for preparing organic glasses with tunable LC order for electronic applications.

Crystallization from solution is a key unit operation utilized across the synthetic scheme to remove impurities. However, little is still known of the underlying impurity purge mechanisms that are responsible for controlling the final purity of the product. Reported herein is the solubility-limited impurity purge mechanism in which the impurity exists as a separate solid phase with its own solubility. A mathematical framework is presented that describes the separation of the impurity in the solid and liquid phases based on the relative solubilities of the product and impurity, and initial impurity level. Three theoretical solubility-limited impurity purge mechanisms are derived that are confirmed experimentally using salicylic acid, ibuprofen, and acetaminophen as model compounds. A practical experimental test is introduced that is used to identify if the impurity is rejected by solubility-limitation and its corresponding type. Finally, development strategies are presented to remove impurities that are purged based on their solubilities.

The mechanisms of purging structurally similar impurities in solution crystallization have been evaluated using the model compound salicylic acid. Of the 11 added impurities, 3 showed appreciable entrapment in the solid phase: viz., salicylamide, anthranilic acid, and benzoic acid. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and the use of a previously reported solubility-limited impurity purge (SLIP) test have shown that the impurities are entrapped by a lattice incorporation mechanism. Impurities become integrated within the product crystals during the crystallization by forming terminal solid solutions. Most of the impurity entrapment was found to take place very early in the crystallization, immediately after seeding. The least entrapment occurred at the end of the crystallization, despite the mother liquor being enriched in impurities. These changes caused purity variations in the solids, which were not properly captured by the average value. A mathematic framework was developed to afford the material impurity distribution (MID), which represents the mass-based impurity profile across a material based on the SLIP test. It is shown that the level of impurities in the crystallized material is far from constant and in fact varies by orders of magnitude, in many cases by more than 20 times. These differences give rise to changes in the physical properties of salicylic acid, as exemplified by a reduction in crystallinity, a lower and broader melting event, and a doubling of solubility.

Previous work has shown that a surface wave on amorphous o-terphenyl (OTP) decays by viscous flow at high temperatures and by surface diffusion at low temperatures. We report that the surface mass transport can be efficiently suppressed by low-concentration polymers. Surface-grating decay has been measured for OTP containing 1 wt % polystyrene (PS, Mw = 1-8 kg/mol), which is miscible with OTP. The additive has no significant effect on the decay kinetics in the viscous-flow regime, but a significant effect in the surface-diffusion regime. In the latter case, surface evolution slows down and becomes nonexponential (decelerating over time). The effect increases with falling temperature and the molecular weight of PS. These results are attributed to the very different mobility of PS (slow) and OTP (fast) and their segregation during surface evolution, and relevant for understanding the surface mobility of multicomponent amorphous materials.

Gelatin nano-coatings can be conveniently applied to amorphous drugs from solution to inhibit fast surface crystallization. Unlike strong polyelectrolyte coatings, a protective gelatin coating does not require strict pairing of opposite charges. This could make gelatin coating a versatile, pharmaceutically acceptable coating for stabilizing amorphous drugs.

Drugs formulated as tablets are subjected to accelerated stability conditions with the goal of identifying a stable formulation that will exhibit a sufficiently long shelf life. Water sorption at a condition such as 40°C/75% RH can result in significant changes in tablet properties such as a decrease in dissolution rate, the cause of which may be difficult to interpret, given the complex nature of ingredients and their interactions in a tablet. In this research, three drugs, displaying a wide range of physicochemical properties, were formulated with commonly used diluents, disintegrants, and binders, using a design of experiments approach. The tablets were stored at accelerated conditions and assessed for content, dissolution, disintegration, and crushing strength, as well as other properties. The research demonstrated many water-induced effects in tablet properties. Due to the experimental design approach that revealed many interactions, it was possible to interpret all of the changes observed in tablet crushing strength, disintegration, and dissolution for the drugs using a common set of physical principles. Specifically, the relevant factors considered were (1) mechanical properties of materials, (2) water sorption surface effects in surface diffusion and capillary condensation, (3) water sorption bulk effects for amorphous materials such as viscous flow/spreading, and (4) water-induced stress on interparticle bonding arising from volume expansion. These physical principles enable a comprehensive interpretation of the complex changes observed in tablet properties, which should be valuable in the design of tablet formulations that will be stable to accelerated storage conditions.

Kinetic arrest of the end-over-end rotation controls the liquid-crystalline order in an organic glass prepared by cooling at different rates, allowing systematic control of molecular packing for electronic applications.

Using high-brilliance high-energy synchrotron X-ray radiation, for the first time the total scattering of a thin organic glass film deposited on a strongly scattering inorganic substrate has been measured in transmission mode. The organic thin film was composed of the weakly scattering pharmaceutical substance indomethacin in the amorphous state. The film was 130 mm thick atop a borosilicate glass substrate of equal thickness. The atomic pair distribution function derived from the thin-film measurement is in excellent agreement with that from bulk measurements. This ability to measure the total scattering of amorphous organic thin films in transmission will enable accurate in situ structural studies for a wide range of materials.