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Handheld NIR Spectroscopy and Hyperspectral Imaging in Combination with Chemometrics for Determination of Active Pharmaceutical Ingredient in Warfarin, Metformin and Nitroglycerin

Bolhassani, Zahra | 2024

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 56941 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Parastar Shahri, Hadi
  7. Abstract:
  8. With the expansion of the pharmaceutical market and the increasing likelihood of distributing substandard medicines, it is necessary to develop methods for rapid, timely, and non-destructive analysis. These methods should enable the assessment of qualitative features such as the amount of active substance and the homogeneous distribution of materials at various stages of drug manufacturing. In this regard, numerous studies have been conducted using spectroscopy and hyperspectral imaging, particularly in the visible and near-infrared regions. The challenge here is that active ingredients in medicine and excipients look very similar in this region. They're usually white powders, and the weak intensity of peaks in this area makes interpreting the data tricky. That's why using advanced methods like chemometrics is crucial for tackling this challenge and extracting useful information. In this research, portable spectrometers and hyperspectral imaging devices in the visible-near-infrared range (400-1000 nm) were utilized. The goal was to determine the active ingredients of nitroglycerin and metformin in powder samples and investigate their homogeneous distribution in tablet formulations. The study also employed data preprocessing methods, curve resolution, and multivariate regression analyses. The determination of the metformin content in a 13-point series, comprising 39 samples with concentrations ranging from 0 to 70.58% by weight of the active ingredient, was conducted using the Radial Basis Function Artificial Neural Network (RBF-ANN) regression on portable spectrometry data. The reported Root Mean Square Error of Prediction (RMSEP) and Coefficient of Determination (R2p) values were 10.74 and 0.8773, respectively. The use of spectral averaging from hyperspectral imaging data with RBF-ANN regression yielded RMSEP and R2p values of 6.36 and 0.9788, respectively. This demonstrated that imaging techniques, particularly when dealing with samples that may not be entirely homogeneous, are highly valuable. Continuing the methodology, the Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) approach was applied to hyperspectral imaging data. Using Support Vector Machine (SVM) regression, the RMSEP and R2p values were reported as 3.35 and 0.9831, respectively, indicating the best performance. All investigations were conducted on a 17-point series, comprising 51 samples that were mixtures of excipients and 10% nitroglycerin in lactose, with weight percentages ranging from 0 to 44.44%. Among these, spectral averaging of hyperspectral imaging data showed the best results with RMSEP and R2p values of 3.04 and 0.9773, respectively, using Partial Least Squares Regression (PLSR). The low weight percentage of nitroglycerin and the increased likelihood of non-uniform distribution made the use of portable spectrometry less effective. Additionally, the spectral correlation between nitroglycerin and excipients was a reason for the less satisfactory results when employing the MCR-ALS method on hyperspectral imaging data. In another section of this research, the application of the MCR-ALS method and the achievement of component distribution maps in heterogeneous samples demonstrated the possibility of studying non-uniform material distribution. The homogeneity levels of metformin tablet samples, with blister, uncovered, and halved, were indicated as 0.9762, 0.9841, and 0.9861, respectively. Similarly, the homogeneity levels of nitroglycerin tablet samples, both intact and halved, were reported as 0.9825 and 0.9827, respectively. Finally, by comparing the results of this study with other research, it was demonstrated that the use of these simple tools, along with employing chemometric methods, can be beneficial for conducting rapid and preliminary analyses to control the quality of pharmaceutical substances
  9. Keywords:
  10. Portable Spectrometry ; Hyperspectral Imaging ; Chemometrics Method ; Multivariate Curve Resolution ; Nitroglycerin ; Metformin

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