Raman measurement in Pharmaceutical industry

I. The application of raman measurement in Pharma industry 

The Raman test method is a non-destructive measurement method that does not need to be processed and separated into substances, which saves measurement time and costs. Raman spectroscopy is a light scattering technique and can be thought of in its simplest form as a process where a photon of light interacts with a sample to produce scattered radiation of different wavelengths, which is used in the various types of pharmaceutical analysis. Superiority of the technique depends upon the molecule of interest, the concentration level, the matrix or solution, other interfering species present, and the desired sampling method. For many applications, it may be a better answer for spectroscopic identification and monitoring needs:

1. Quantitative analysis of pharmaceutical dosage formulations

The two main advantages of using Raman spectroscopy over other spectroscopic techniques are its sampling simplicity and information content. It is known that Raman scattering is proportional to the concentration of the analyzed substance and due to the same, Raman spectroscopy can be used for quantitative analysis. Variable factors in quantitative analysis by Raman spectroscopy include excitation intensity, sample positioning and temperature fluctuations, which strongly affect the precision and detection limit values. Accurate quantitative information can be obtained by using either an internal or external standard.

2. Identification of polymorphs

Polymorphs are simply different crystal forms of a single molecular entity that have different arrangements and/or conformation of the molecules in the crystal lattice. Polymorphism may also include solvation or hydration products (also known as pseudopolymorphs) and amorphous forms. The analysis of polymorphs is the application that made Raman spectroscopy a standard part of the instrumental toolbox when low wavenumber Raman scattering below 200cm-1 can also be related to the polymorphism behavior of active pharmaceuticals.

3. Monitoring real-time processes in the pharmaceutical industry

Raman has the potential to give valuable insight into process understanding, optimization and monitoring when used in development and scale-up operations. It is used to quantify changes in-situ during processes such as wet granulation and batch crystallization. Quantitative and qualitative trends can be assessed, and adjustments can be made quickly during routine processing based on Raman analysis.

4. Detection of counterfeit and adulterated pharmaceutical products

The increase in the counterfeiting of pharmaceutical drugs is becoming a concern as it can damage health by supplying inappropriate substances or products. Raman Spectroscopy is frequently used technique by the FDA’s Forensic Chemistry Centre (FCC) for the analysis of suspect counterfeit products as it allows for the qualitative identification of both API and excipients used to manufacture the product. The Raman spectra of an authentic tablet coating and core can be used as a “spectral fingerprint” for a suspected counterfeit product.

Figure 1: (a) Raman spectrum of a suspect counterfeit tablet coating, (b) Raman spectrum of an authentic tablet coating.

It is very clear that some additional peaks are observed in the Raman spectrum of the suspect counterfeit tablet coating and that is not observed in the authentic product tablet coating.

Figure 2: . (a) Raman spectrum of a suspect counterfeit tablet core, (b) Raman spectrum of an authentic tablet core

5. Raman chemical imaging of solid dosage formulations

Vibrational spectroscopic methods, such as Near Infrared (NIR) absorption or reflectance and Raman spectroscopy, combined with imaging are particularly useful for analysis of pharmaceutical forms. The rapid, non-destructive, and noninvasive features of chemical imaging mark its potential suitability as a Process Analytical Technology (PAT) in the pharmaceutical industry for identification of critical control parameters that impact on finished product quality. It can be applied to study the physical forms of potent API present in dosage forms like creams and ointments, for investigations of active and excipients distribution in granules and in probing amorphous solid dispersion formulations for phase separation.

Figure 3:Composite Raman image comparing data from two tablets with the same overall composition but different formulation protocols.

The solubility of this API in the Lutrol binder was relatively low, which lead to non-uniform distribution of API in the granules and ultimately non-uniform distribution of API in the tablets prepared from them (Figure3 - left). The corresponding image with higher uniformity of colour is one where the API was first dissolved in binder and the resulting mass was regrounded before granulation in a fluidized bed as before (Figure 3- right).

Though the amount of API was same in both the formulation, by examining the cross section of tablet, distribution of API in particular formulation can be easily analyzed using Raman chemical imaging without any sample preparation. Raman chemical imaging was suitable for distinguishing between active samples and placebos. It was noted, however, that vigorous validation of Raman- chemical imaging for particle size distribution was required, due to the high variability associated with replicate measurements.

II. Spectrometers recommendations:

The most important part of modular Raman setup is the spectrometer. Our high-performance QE Pro-Raman spectrometer, with excellent sensitivity and throughput over a wide spectral range, to the recently introduced Ocean HDX Raman spectrometer will be the potential options with an affordable budget for researchers and product integrators. Besides, the Fiber Optics Raman Probes, Raman Lasers and Raman Accessories are also available to serve the requirements of customers’ applications.

 Keywords: Raman spectroscopy, pharmaceutical industry, raman measurement, QE Pro-Raman, Ocean HDX Raman, Raman Probe