In-line UV spectroscopy for the quantification of low-dose active ingredients during the manufacturing of pharmaceutical semi-solid and liquid formulations

Abstract

UltraViolet (UV) spectroscopy was evaluated as an innovative Process Analytical Technology (PAT) - tool for the in-line and real-time quantitative determination of low-dosed active pharmaceutical ingredients (APIs) in a semi-solid (gel) and a liquid (suspension) pharmaceutical formulation during their batch production process. The performance of this new PAT-tool (i.e., UV spectroscopy) was compared with an already more established PAT-method based on Raman spectroscopy. In-line UV measurements were carried out with an immersion probe while for the Raman measurements a non-contact PhAT probe was used. For both studied formulations, an in-line API quantification model was developed and validated per spectroscopic technique. The known API concentrations (Y) were correlated with the corresponding in-line collected preprocessed spectra (X) through a Partial Least Squares (PLS) regression. Each developed quantification method was validated by calculating the accuracy profile on the basis of the validation experiments. Furthermore, the measurement uncertainty was determined based on the data generated for the determination of the accuracy profiles. From the accuracy profile of the UV- and Raman-based quantification method for the gel, it was concluded that at the target API concentration of 2% (w/w), 95 out of 100 future routine measurements given by the Raman method will not deviate more than 10% (relative error) from the true API concentration, whereas for the UV method the acceptance limits of 10% were exceeded. For the liquid formulation, the Raman method was not able to quantify the API in the low-dosed suspension (0.09% (w/w) API). In contrast, the in-line UV method was able to adequately quantify the API in the suspension. This study demonstrated that UV spectroscopy can be adopted as a novel in-line PAT-technique for low-dose quantification purposes in pharmaceutical processes. Important is that none of the two spectroscopic techniques was superior to the other for both formulations: the Raman method was more accurate in quantifying the API in the gel (2% (w/w) API), while the UV method performed better for API quantification in the suspension (0.09% (w/w) API).

Raman Spectroscopy for Quantitative Analysis in the Pharmaceutical Industry

“…Predictive results for method performance (R 2 = 0.973; Q 2 = 0.973; RMSECV = 0.0418% w/w) were obtained even in a low concentration. On three different days, RMSEP values of 0.0255, 0.0235 and 0.0381% (w/w) for three validation sets were obtained (81). These results evidence the capability of the technique to evaluate the mixtures of different pharmaceutical forms (solid, semisolid, and liquid).…”

A Process Analytical Technology (Pat) Approach to Evaluate Gabapentin Distribution in Laminar Extrudates

“…Current trends in pharmaceutical industry are focused on the application of fast and non-destructive techniques for on-line process monitoring and evaluation the drug product quality. By using advanced non-invasive analytical techniques, it is possible to closely monitor the pharmaceutical manufacturing process [3,4,15,24,26]. This approach is in accordance with the Process and Analytical Technology (PAT) strategy which is currently recommended by regulatory authorities such as the European Medicines Agency and US Food and Drug Administration [9,10,12].…”

Herbal Medicine Characterization Perspectives Using Advanced FTIR Sample Techniques – Diffuse Reflectance (DRIFT) and Photoacoustic Spectroscopy (PAS)

“…The chemical composition of herbs may vary depending on the species, location of growth, age, harvesting season, drying conditions, and other factors (Heinrich, 2015). Therefore, comprehensive studies of effective analytical methods are required to make quick and reliable quality control at any stage of herbal medicine (HM) production as well as during the storage process, to obtain feedback (Bostijn et al, 2018;Rehrl et al, 2018).…”