Measuring Interfacial Polymerization Kinetics Using Microfluidic Interferometry.

A range of academic and industrial fields exploit interfacial polymerization in producing fibers, capsules, and films. Although widely used, measurements of reaction kinetics remain challenging and rarely reported, due to film thinness and reaction rapidity. Here, polyamide film formation is studied using microfluidic interferometry, measuring monomer concentration profiles near the interface during the reaction. Our results reveal that the reaction is initially controlled by a reaction-diffusion boundary layer within the organic phase, which allows the first measurements of the rate constant for this system.

Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery.

Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, we outline several approaches in designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs, highlighting polymer-drug formulation guidelines from industrial and academic perspectives. Special attention is given to new commercial and specialized polymer design strategies that can solubilize highly hydrophobic APIs and suppress the propensity for rapid drug recrystallization. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.

A framework for multi-scale simulation of crystal growth in the presence of polymers.

We present a multi-scale simulation method for modeling crystal growth in the presence of polymer excipients. The method includes a coarse-grained (CG) model for small molecules of known crystal structure whose force field is obtained using structural properties from atomistic simulations. This CG model is capable of stabilizing the molecular crystal structure and capturing the crystal growth from the melt for a wide range of small organic molecules, as demonstrated by application of our method to the molecules isoniazid, urea, sulfamethoxazole, prilocaine, oxcarbazepine, and phenytoin. This CG model can also be used to study the effect of additives, such as polymers, on the inhibition of crystal growth by polymers, as exemplified by our simulation of suppression of the rate of crystal growth of phenytoin, an active pharmaceutical ingredient (API), by a cellulose excipient, functionalized with acetate (Ac), hydroxy-propyl (Hp) and succinate (Su) groups. We show that the efficacy of the cellulosic polymers in slowing crystal growth of small molecules strongly depends on the functional group substitution on the cellulose backbone, with the acetate substituent group slowing crystal growth more than does the deprotonated succinate group, which we confirm by experimental drug supersaturation studies.

Collective Rayleigh-Plateau Instability: A Mimic of Droplet Breakup in High Internal Phase Emulsion.

Using a microfluidic multi-inlet coflow system, we show the Rayleigh-Plateau instability of adjacent, closely spaced fluid threads to be collective. Although droplet size distributions and breakup frequencies are unaffected by cooperativity when fluid threads are identical, breakup frequencies and wavelengths between mismatched fluid threads become locked due to this collective instability. Locking narrows the size distribution of drops that are produced from dissimilar threads, and thus the polydispersity of the emulsion. These observations motivate a hypothesized two-step mechanism for high internal phase emulsification, wherein coarse emulsion drops are elongated into close-packed fluid threads, which break into smaller droplets via a collective Rayleigh Plateau instability. Our results suggest that these elongated fluid threads break cooperatively, whereupon wavelength-locking reduces the ultimate droplet polydispersity of high-internal phase emulsions, consistent with experimental observations.

Surface shear inviscidity of soluble surfactants.

Foam and emulsion stability has long been believed to correlate with the surface shear viscosity of the surfactant used to stabilize them. Many subtleties arise in interpreting surface shear viscosity measurements, however, and correlations do not necessarily indicate causation. Using a sensitive technique designed to excite purely surface shear deformations, we make the most sensitive and precise measurements to date of the surface shear viscosity of a variety of soluble surfactants, focusing on SDS in particular. Our measurements reveal the surface shear viscosity of SDS to be below the sensitivity limit of our technique, giving an upper bound of order 0.01 µN·s/m. This conflicts directly with almost all previous studies, which reported values up to 10(3)-10(4) times higher. Multiple control and complementary measurements confirm this result, including direct visualization of monolayer deformation, for SDS and a wide variety of soluble polymeric, ionic, and nonionic surfactants of high- and low-foaming character. No soluble, small-molecule surfactant was found to have a measurable surface shear viscosity, which seriously undermines most support for any correlation between foam stability and surface shear rheology of soluble surfactants.