Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing.

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.

Synthesis and preliminary pharmacology of an internal standard for assay of neostigmine.

The synthesis of the diethyl analog of neostigmine, its preliminary pharmacology, and its use as an internal standard for the GLC assay of neostigmine are described. Both the diethyl analog and neostigmine undergo thermal demethylation in the injection port. The column selected produced satisfactory resolution and short retention times for neostigmine and the diethyl analog. The diethyl analog apparently possesses acetylcholinesterase-inhibiting properties, as evidenced by potentiation of the contractile response to acetylcholine in the ileum. In addition, acetylcholine levels in the brain were elevated slightly. Water solutions of the diethyl analog appeared to lose biological activity with time. the diethyl analog appears to be suitable for use as an internal standard for the GLC assay of neostigmine.