Continuous-flow technology is devised and implemented for manufacture of a drug candidate in clinical trials.

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.

The electrohydrodynamic stability of a liquid bridge was studied in steady and oscillatory axial electric fields with a novel apparatus aboard a space shuttle. To avoid interphase transport, which complicates matters in terrestrial, matched-density systems, the experiments focused on a liquid column surrounded by a dielectric gas. The micro-gravity acceleration level aboard the spacecraft kept the Bond number small; so interface deformation by buoyancy was negligible. To provide microgravity results for comparison with terrestrial data, the behaviour of a castor oil bridge in a silicone oil matrix liquid was studied first. The results from these experiments are in excellent agreement with earlier work with isopycnic systems as regards transitions from a perfect cylinder to the amphora shape and the separation of an amphora into drops. In addition, the location of the amphora bulge was found to be correlated with the field direction, contrary to the leaky dielectric model but consistent with earlier results from terrestrial experiments. Next, the behaviour of a bridge surrounded by a dielectric gas, sulphur hexa fluoride (SF6), was investigated. In liquid–gas experiments, electrohydrodynamic ejection of liquids from ‘Taylor cones’ was used to deploy fluid and form bridges by remote control. Experiments with castor oil bridges in SF6 identified the conditions for two transitions: cylinder–amphora, and pinch-off. In addition, new behaviour was uncovered with liquid–gas interfaces. Contrary to expectations based on perfect dielectric behaviour, castor oil bridges in SF6 could not be stabilized in AC fields. On the other hand, a low-conductivity silicone oil bridge, which could not be stabilized by a DC field, was stable in an AC field.