462188 Raman Mapping for Analyzing Multi-Component Solid Dosage Formulations

Friday, November 18, 2016: 2:10 PM
Continental 5 (Hilton San Francisco Union Square)
Zhen Liu, Pharmaceutical Research & Development, Merck & Co., Inc., West Point, PA, Haichen Nie, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, Patrick Marsac, College of Pharmacy, University of Kentucky, Lexington, KY; Pharmaceutical Sciences, Merck & Co., Inc., West Point, PA, Brian Marks, Analytical Sciences, Merck & Co., Inc., West Point, PA, Wei Xu, Preformulation, Merck Research Laboratories, Merck & Co., Inc., West Point, PA and Anthony Leone, Preformulation Sciences, Merck & Co., Inc., West Point, PA

It has always been challenging to use spectroscopic methods to analyze salt disproportionation in a multi-component tablet matrix due to the spectral interference generated by the various excipients. Although combining Raman spectroscopy and chemometrics can be a powerful approach to study the extent of salt disproportionation, it was found in the present study that bulk measurements and chemometric modeling have obvious limitations when the targeted component is present at low levels in the tablet. Hence, a two-step Raman mapping approach was developed herein to investigate salt disproportionation in tablets with a low drug loading (5% w/w). The first step is to locate the area of interest where the drug particles reside throughout the tablet surface by using a statistically optimized sampling method termed deliberate sub-sampling. The second step, referred to herein as close-step mapping, utilize a step by step mapping of the targeted area to find more details of salt disproportionation in the tablet regions where the drug is concentrated. By using this two-step Raman mapping approach, we successfully detected the existence of minor species embedded in multi-component low drug loading tablet matrices, where bulk measurements from routine techniques usually lack of sensitivity. This approach will help formulation scientists detect and understand salt disproportionation and in situ drug-excipients compatibility issues in low dose solid dosage formulations.

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