(M1130-10-56) Near-Infrared Assessment: A Potential Rapid Screening Tool for Pharmaceutical Quality Assessment

Purpose: Near-infrared (NIR) spectrometers are one of the efficient process analytical technologies (PAT). NIR has been commercially available since the 1940s. NIR is a technique based on the vibrations of the atoms of a molecule (1). NIR saves the product integrity as it needs no sample preparation. NIR spectrometers can be used to analyze a wide variety of products, including powder, liquid, and all kinds of solid products, and act as a “fingerprint” scanner. Hanse, NIR can be used to differentiate between pure (original) and adulterated products, check the homogeneity of batches, and distinguish counterfeit products. The goal of this research project is to introduce the NIR analysis as a recommended pharmacopeial qualitative and quantitative tool for rapid evaluation of intra/inter batch variability for both single small pharmaceutical molecules & natural supplements with multiple active pharmaceutical components.

Methods: Three categories of pharmaceutical products and nutraceuticals, including levothyroxine tablets, weight loss nutraceuticals, and male enhancement nutraceuticals were selected to be fully evaluated via pharmacopeial and NIR assessment. Triplicate packages of three batches of four weight loss brands (W1 to W4), five male enhancement brands (E1 to E5), and three levothyroxine sodium brands (T1 to T3) were purchased and analyzed. Pharmacopeial tests namely, content uniformity, dissolution, disintegration, stability, weight variation, hardness, thermal analysis, and/or friability were conducted to investigate the safety and efficacy parameters. All pharmacopeial tests were conducted according to the method described in the USP < 905 > and British Pharmacopoeia Commission, 2014c. Regarding NIR analysis, NIR spectra were recorded on Bruker^TM near-infrared spectroscopy (Bruker-MPA, Germany). Measurements were carried out with an optical resolution of 16 cm^-1 and 32 cm^-1 over the 4000-9000 cm¹ spectra range.

Results: Comprehensive collective NIR spectra of all products together were collected (Figure 1). The percentage correlation cutoff used, which indicates uniformity and consistency within each product, is 96%. For weight loss products, the percentage of identical capsules (96% correlation) across different batches of Brand W1 to W4 were 62.7%, 28.1%, 48.6%, and 45.8%, respectively (Figure 2). The pharmacopeial test findings supported the NIR screening for all tested products. All the tested batches that failed to pass the NIR evaluation, did not pass the conducted pharmacopeial assessment. As a representative example, HPLC analyses showed high variability of drug content for all the NIR failed tested products (Figure 3). The mean values of drug content in different batches of weight loss Brand W1 ranged from 101.57±164.31 to 4.50 ± 2.49 mg while its NIR correlation was 62.7%. Therefore, both NIR & HPLC analysis of Brand W1 confirmed its inter-batch variability. For male enhancement products, the percentage of identical tablets (96% correlation) across different batches of Brand E1 to E6 were 100%, 50%, 29%, 67%, 77%, and 65%, respectively. The content uniformity of male enhancement, Brand E1 was 99.10±6.1 and its NIR screening showed a 100% NIR correlation of identical tablets across different batches. On the other hand, the mean values of drug content Brands E2 to E6 ranged from 48.4±21.8 to 76±46, 25.9±37.4 to 52.5±36.9, 11.2±16.8 to 22.2±19.1, 78±10.7 to 78.7±9.6, and 62.1±25.9 to 64.3±28.2 mg, respectively. Therefore, their pharmacopeia content uniformity results aligned with their NIR analyses. All the tested male enhancement products failed the content uniformity limit & NIR correlation cutoff except Brand E1 (Figure 2&3). For levothyroxine products, the percentage of identical tablets (96% correlation) across different batches of Brand T1 to T3 were 78%, 52.3%, and 37.5%, respectively (Figure 2). The levothyroxine Brand T3 failed to pass the BP pharmacopeia dissolution limit (75% at 45 min) as its dissolution was 62.62% at 45 min. Therefore, the pharmacopeial dissolution results were also aligned with NIR screening.

Conclusion: The reported results of both NIR & performed pharmacopeial tests aligned together. NIR screening could be a potential tool that can be implemented for a rapid and reproducible quality assessment tool to support intra/inter batch variability/sameness, bioequivalence, and/or post-marketing approval to facilitate the regulatory approval pathway.

References: 1.​ Stuart BH. Introduction, in Infrared Spectroscopy: Fundamentals and Applications. S.L: John Wiley & Sons; 2005.
2.​ Abbas O, P., Dardenne, V. Baeten. Chapter 3 - Near-Infrared, Mid-Infrared, and Raman Spectroscopy, in Chemical Analysis of Food: Techniques and Applications. Y. Picó, editor: Academic Press: Boston.
3. ​da Silva NC, Honorato RS, Pimentel MF, Garrigues S, Cervera ML, de la Guardia M. Near Infrared Spectroscopy Detection and Quantification of Herbal Medicines Adulterated with Sibutramine. Journal of Forensic Sciences. 2015;60(5):1199-205.
4.​ Kalyanaraman R, Dobler G, Ribick M. Near-Infrared (NIR) Spectral Signature Development and Validation for Counterfeit Drug Detection Using Portable Spectrometer. American Pharmaceutical Review. 2011;14(4):98-104.

Acknowledgements: Nada Helal

Figure 1: NIR Spectra for different batches of weight loss brands (Brand W1 to Brand W4), male enhancement brands (Brand E1 to Brand E5), and levothyroxine sodium brands (Brand T1 to Brand T3). Measurements were carried out with an optical resolution of 16 cm-1 and 32 cm-1 over the spectra range 9000-4000 cm-1.

Figure 2: Percentage Correlation within each brand of weight loss brands (A) (Brand W1 to W4), (B) male enhancement brands (Brand E1 to E5), and (C) levothyroxine brands (Brand T1 to T3) as reported by NIR analysis. Green & Red shaded areas represent a correlation within each brand of more than 96 & less than 96%, respectively.

Figure 3: Pharmacopeial drug content assessment for different batches of (A) Weight loss products (Brand W1 to W4), (B) Male enhancement products (Brand E1 to E6) analyzed via High Performance Chromatography (HPLC).