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DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai), INDIA, worlddrugtracker, 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.8 Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contributionn, सुकून उतना ही देना प्रभू, जितने से जिंदगी चल जाये।औकात बस इतनी देना,कि औरों का भला हो जाये।...........P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

Showing posts with label Application. Show all posts

Sunday, 6 March 2016

Application of On-Line NIR for Process Control during the Manufacture of Sitagliptin

The transamination-chemistry-based process for sitagliptin is a through-process, which challenges the crystallization of the active pharmaceutical ingredient (API) in a batch stream composed of multiple components. Risk-assessment-based design of experiment (DoE) studies of particle size distribution (PSD) and crystallization showed that the final API PSD strongly depends on the seeding-point temperature, which in turn relies on the solution composition.

To determine the solution composition, near-infrared (NIR) methods had been developed with partial least squares (PLS) regression on spectra of simulated process samples whose compositions were made by spiking each pure component, either sitagliptin free base (FB), water, isopropyl alcohol (IPA), dimethyl sulfoxide (DMSO), or isopropyl acetate (IPAc), into the process stream according to a DoE. An additional update to the PLS models was made by incorporating the matrix difference between simulated samples in lab and factory batches.

Overall, at temperatures of 20–35 °C, the NIR models provided a standard error of prediction (SEP) of less than 0.23 wt % for FB in 10.56–32.91 wt %, 0.22 wt % for DMSO in 3.77–19.18 wt %, 0.32 wt % for IPAc in 0.00–5.70 wt %, and 0.23 wt % for water in 11.20–28.58 wt %. After passing the performance qualification, these on-line NIR methods were successfully established and applied for the on-line analysis of production batches for compositions prior to the seeding point of sitagliptin crystallization.

see.........

http://pubs.acs.org/doi/abs/10.1021/acs.oprd.5b00409