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.

Separation and structure determination of nicardipine photoproducts by LC-ESI-MS.

A sample of 0.104 M nicardipine in methanol was photoirradiated with a Philips 400 W UV lamp for 3 h in a photochemical chamber. A total of four major photoproducts were found from the HPLC chromatogram. The same sample was used for taking LC-MS, while eight major photoproducts were observed and the structures elucidated by analyzing the CID patterns of their respective mass spectra. A reaction scheme of nicardipine is proposed that the photochemical reactions occur mainly via oxidation of 1,4-dihydropyridine moiety, following the stepwise photo-reduction of the m-nitro group and demethylation of the ester group at 5-position of the pyridine ring.

The difference between nicardipine and its enantiomers on inhibiting vasoconstriction of isolated rabbit thoracic artery.

The present study was designed to study the difference effects between nicardipine and its two enantiomers on thoracic artery of rabbit. A high-performance liquid chromatographic method was used to prepare the two enantiomers of nicardipine. The thoracic artery of rabbit was removed. The vessels were cut into 3 mm in width and 15 mm in length spiral strips and immersed into tissue baths. The concentration-response curves of nicardipine and its enantiomers were obtained by cumulative administration of the vasoconstrictors. Nicardipine and the enantiomers could shift the dose-response curves of NE, KCl or CaCl2 to right in a nonparallel manner and decrease the maximum effective in a concentration-depended manner, respectively. The pD2' value of R-(-)-nicardipine showed significantly effective than that of nicardipine and S-(+)-nicardipine (P<0.01). There was not obviouse difference between the pD2' value of nicardipine and S-(+)-nicardipine (P>0.05). The results demonstrate that the stereoselective interaction between R-(-)-nicardipine and L-calcium channel receptor is more stronger than that of S-(+)-nicardipine.

Investigation and optimisation of the use of micellar electrokinetic chromatography for the analysis of six cardiovascular drugs.

A micellar electrokinetic chromatography method was optimised for the separation of the six cardiovascular drugs atenolol, nicardipine, nifedipine, diltiazem, verapamil, and amlodipine by investigating the effects of pH, sodium dodecyl sulphate (SDS) concentration, selection and concentration of organic modifier. An electrophoresis buffer of 100 mM borate pH 8.1 containing 50 mM SDS and 15% (v/v) acetone was found to provide the optimum separation with respect to resolution and migration time.