Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation.

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

The objective of the present in vitro study was to investigate cardiomyocyte functions, specifically their adhesion and proliferation, on injectable scaffolds containing RNT (rosette nanotubes) and CNF (carbon nanofibers) in a pHEMA (poly(2-hydroxyethyl methacrylate)) hydrogel to determine their potential for myocardial tissue engineering applications. RNTs are novel biocompatible nanomaterials assembled from synthetic analogs of DNA bases guanine and cytosine that self-assemble within minutes when placed in aqueous solutions at body temperatures. These materials could potentially improve cardiomyocyte functions and solidification time of pHEMA and CNF composites. Because heart tissue is conductive, CNFs were added to pHEMA to increase the composite's conductivity. Our results showed that cardiomyocyte density increased after 4 h, 1 day, and 3 days with greater amounts of CNFs and greater amounts of RNTs in pHEMA (up to 10 mg mL(-1) CNFs and 0.05 mg mL(-1) RNTs). Factors that may have increased cardiomyocyte functions include greater wettability, conductivity, and an increase in surface nanoroughness with greater amounts of CNFs and RNTs. In effect, contact angles measured on the surface of the composites decreased while the conductivity and surface roughness increased as CNFs and RNTs content increased. Lastly, the ultimate tensile modulus decreased for composites with greater amounts of CNFs. In summary, the properties of these injectable composites make them promising candidates for myocardial tissue engineering applications and should be further studied.

Technological advances have an important role in the design of greener synthetic processes. In this Personal Account, we describe a wide range of thermal, photochemical, catalytic, and biphasic chemical transformations examined by our group. Each of these demonstrate how the merits of a continuous flow synthesis platform can align with some of the goals put forth by the Twelve Principles of Green Chemistry. In particular, we illustrate the potential for improved reaction efficiency in terms of atom economy, product yield and reaction rates, the ability to design synthetic process with chemical and solvent waste reduction in mind as well as highlight the benefits of the real-time monitoring capabilities in flow for highly controlled synthetic output.