Raman spectroscopy: troubleshooting in the manufacture of Nadolol

Jack Melton; Luis Collazo; Christiane Rodriguez; Paul Findlay

doi:10.1117/12.345382

9 April 1999 Raman spectroscopy: troubleshooting in the manufacture of Nadolol

Jack Melton, Luis Collazo, Christiane Rodriguez, Paul Findlay

Proceedings Volume 3608, Biomedical Applications of Raman Spectroscopy; (1999) https://doi.org/10.1117/12.345382
Event: BiOS '99 International Biomedical Optics Symposium, 1999, San Jose, CA, United States

Abstract

The manufacture of Nadalol at our facilities in Humacao, Puerto Rico, poses a difficult challenge for process analysis because the highly toxic epichlorohydrin makes routine analysis of the chemistry very hazardous. Raman spectroscopy enables us to gather potentially quantifiable and irrefutable data from samples without exposing manufacturing personnel to any hazard. The reaction of epichlorohydrin and sodium (CTA) phenolate monitored by Raman spectroscopy measures both the presence of CTA, epichlorohydrin and tert-butylamine. The Raman shifts of epichlorohydrin at 400-350 cm^-1 and sodium at 1630- 1560 cm^-1 were easily discernible and useful. On one occasion, the increase of moisture in this mixture alerted plant operators to verify the extent of this unexpected contamination. In a short time, optimization of these three aspects with one technique resulted in reliable performance for this stage of the process. The final stage of the process is isolation of the drug substance by crystallization and we learned that this step is strongly influenced by residual tert-butylamine. Using the Raman technique, the presence of this amine is easily detected and accommodated in real time prior to crystallization.

Citation Download Citation

Jack Melton, Luis Collazo, Christiane Rodriguez, and Paul Findlay "Raman spectroscopy: troubleshooting in the manufacture of Nadolol", Proc. SPIE 3608, Biomedical Applications of Raman Spectroscopy, (9 April 1999); https://doi.org/10.1117/12.345382

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