Automation of Continuous Albuterol Synthesis

Albuterol is a bronchodilator found in inhalers that works by relaxing the airways in the lungs. Albuterol sulfate is on the FDA drug shortage list, motivating more efficient synthesis techniques. Continuous manufacturing is less time- and resource-intensive than traditional batch production. By integrating automation, product quality is more easily controlled and monitored, allowing for modular, small-scale, distributed manufacturing. The continuous synthesis process for albuterol involves multiple unit operations, including distillation, hydrogenation through a packed bed reactor, and process analytical technology (PAT) monitoring to determine whether the product is within specified quality conditions. The distillation column operation was automated by integrating flow and weight monitoring to maintain steady state, as well as automatically toggling a valve to target a specified reflux ratio. On-line monitoring of pressure drop across a packed-bed reactor and waste diversion was demonstrated. A flow loop was set up to monitor pH and NMR spectra of a product stream with varying concentrations of the impurity tert-butylamine. In addition, an experimental setup was devised for the automated calibration of peristaltic pumps. Code was written in Python and implemented with a Raspberry Pi, which handled all data collection, actuation, and process control. Future work aims to implement feedback loops which will use process data from later stages to change operating conditions earlier on in the system.