ABSTRACT
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.
Subject(s)
Chemistry, Pharmaceutical/methods , Pharmaceutical Preparations/chemical synthesis , Diazepam/chemical synthesis , Diazepam/standards , Diphenhydramine/chemical synthesis , Diphenhydramine/standards , Lidocaine/chemical synthesis , Lidocaine/standards , Pharmaceutical Preparations/standards , Pharmacopoeias as TopicABSTRACT
In this study, the potential of biobutanol was evaluated as an alternative to bioethanol which is currently the predominant liquid biofuel in the US. Life-cycle assessments (LCAs) suggest that the net energy generated during corn-to-biobutanol conversion is 6.53 MJ/L, which is greater than that of the corn-derived bioethanol (0.40 MJ/L). Additionally, replacing corn with lignocellulosic materials in bioethanol production can further increase the net energy to 15.90 MJ/L. Therefore, it was interesting to study the possibility of using domestically produced switchgrass, hybrid poplar, corn stover, and wheat straw as feedstocks to produce liquid biofuels in the US. By sustainable harvest based on current yields, these materials can be converted to 8.27 billion gallons of biobutanol replacing 7.55 billion gallons of gasoline annually. To further expand the scale, significant crop yield increases and appropriate land use changes are considered two major requirements.
