Quanlity Control In The Pharmaceutical Industry By Raman Spectroscopy

INTRODUCTION

Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. The World Health Organization reports that 25% to 50% of cases in developing countries involve the purchase of undeclared drugs, which are often counterfeit. Low-quality medication may fail to achieve the desired effect or even cause harm to the patient and is commonly found in today's pharmaceutical market. Quality control in the pharmaceutical industry is complicated by factors such as complex manufacturing processes, packaging, storage, and aging.

Raman spectroscopy has been widely used in pharmaceutical analysis. Pills or tablets can be measured through blisters providing the pharmaceutical industry with a fast and non-destructive method for quality control. Identification and quantification of polymorphs in powders can also be done, which can be of extreme help when one of the polymorphs is not active or has an adverse effect. Thus, Raman spectroscopy provides the advantages of being a non-destructive, fast, easy, water-insensitive, and inexpensive technique, which can not only be useful to the pharmaceutical industry for quality control but also for law enforcement agents involved in actions to detect and seize counterfeit drugs.

METHODS

By interacting light with chemical bonds in the material, the Raman spectrum shows peaks that represent the intensity and wavelength position of the Raman scattered light, with each peak corresponding to a specific molecular bond vibration. This provides detailed information about chemical structure, phase, polymorphism, crystallinity, and molecular interactions.

Figure 1 is the Raman spectrum of acetaminophen and its degradant: p-aminophenol. The structures of acetaminophen and its breakdown products are quite different and thus produce Raman spectra with significant differences from which the mixture can be quantified.

The Raman spectrum of acetaminophen is dominated by peaks at 797, 858, 1236, 1324, 1560, 1611, and 1649 cm^-1, which are assigned to CNC ring stretching, ring breathing, C–C ring stretching, amide III, amide II, ring stretching, and amide I modes, respectively. Upon loss of the amide functional group during degradation, the amide bands and the CNC stretching mode disappear, while the increased molecular symmetry results in more intense ring modes for p-aminophenol.

Figure 1: Raman spectra of (a) acetaminophen and (b) p-aminophenol.

The preprocessing of spectral data is essential for noise removal and the reduction and elimination of variability in the data that is not related to the property of interest, all to enable the examined spectra to be further modeled more effectively. Careful selection of the spectral preprocessing algorithm can improve the robustness and quality of the final model.

The Raman spectrum is prone to baseline shifts, scattering effects, and noise, which affect its interpretability. The different spectral preprocessing algorithms correspond to different functions: smoothing, minimizing noise effects, removing gradient shifts, and correcting dispersion effects. However, it is important to establish a balance between the various preprocessing steps to ensure that key spectral features are not lost or distorted, maintaining the integrity and relevance of the spectral data for accurate analysis.

Figure 2: Raman spectra of p-aminophenol mixed with acetaminophen at 100, 50, 20, 10, 5, and 2 mass %.

Pharmaceuticals can break down faster and lose their effectiveness before they expire, and some breakdown products can be toxic. Now evaluate whether this pharmaceutical has been degraded or not through raman spectroscopy by mixing pure acetaminophen with its own degradation product (p-aminophenol) at different concentrations (Figure 2). The analysis results are evaluated in Table 1.

It is clear from these data, that traditional peak height analysis will not allow accurate determination of acetaminophen in a medication that has degraded by 10% or less. Due to the complexity and enormous amount of information obtained from Raman spectroscopy, it is uncertain whether univariate processing methods are sufficient to choose as calibration models. Therefore, it is necessary to apply multivariate processing algorithms to understand and determine the relevance of data originating from multiple variables. Both spectral types yielded more accurate concentrations than the simple peak height calculation. More importantly, the spectra-based calculated percentages proved very accurate at the low concentrations, e.g., 4.9% and 2.2% for 5.0% and 2.0%, respectively.

Table 1: Prepared and Calculated percentages of p-aminophenol mixed with acetaminophen determined using Raman peak height at 846 cm−1 and spectral weighting of the spectra and their first derivatives for the 550 to 1800 cm−1 region.

BUILD SYSTEM

INTINS can provide a complete system for this application. The Ocean HDX Raman spectrometer is a compact, high-performance spectrometer for 785 nm Raman excitation applications. This small-footprint instrument unlocks Raman signature data from 150 cm-1 to 3400 cm-1, is available with a 25 µm or 50 µm entrance slit, and can be combined with a laser, probe, and sample holder to measure solids, powders, and liquids.

Less expensive than traditional scientific-grade Raman instruments yet sacrificing very little in performance, Ocean HDX Raman is within reach to a wider range of users, including university teaching and research labs, budget-limited start-ups, and anyone that appreciates great value. In addition, Ocean HDX Raman is attractive for integration into other products, offering the advantages of small size and lightweight, plus thermal stability, and Ethernet connectivity.

Ocean Insight offers a variety of 785 nm Raman lasers, commonly used in Raman spectroscopy. The 785 nm wavelength is particularly popular because it offers a good balance between fluorescence suppression (common with shorter wavelengths) and Raman signal intensity (which decreases with longer wavelengths).

These lasers are designed to provide a stable and precise 785 nm wavelength, which is essential for high-precision Raman measurements. Raman lasers also provide different output power levels to suit each user's specific application. It is designed to integrate seamlessly with Ocean Insight's wide range of Raman spectrometers and accessories.