- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Transmission Low-Frequency Raman Spectroscopy for Quantification of Crystalline Polymorphs in Pharmaceutical Tablets
摘要： The purpose of this study was to quantify polymorphs of active pharmaceutical ingredients in pharmaceutical tablets using a novel transmission low-frequency Raman spectroscopy method. We developed a novel transmission geometry for low-frequency Raman spectroscopy and compared quantitative ability in transmission mode versus backscattering mode using chemometrics. We prepared two series of tablets: 1) containing different weight-based contents of carbamazepine form III and 2) including different ratios of carbamazepine polymorphs (forms I/ III). From the relationship between the contents of carbamazepine form III and partial least squares (PLS) predictions in the tablets, correlation coefficients in transmission mode (R2= 0.98) were found to be higher than in backscattering mode (R2= 0.97). The root mean square error of cross-validation (RMSECV) of the transmission mode was 3.9 compared to 4.9 for the backscattering mode. The tablets containing a mixture of carbamazepine (I/ III) polymorphs were measured by transmission low-frequency Raman spectroscopy, and it was found that the spectral shape changed according to the ratio of polymorphs: the relationship between the actual content and the prediction showed high correlation. These findings indicate that transmission low-frequency Raman spectroscopy possess the potential to complement existing analytical methods for the quantification of polymorphs.
关键词： Transmission,Carbamazepine,Pharmaceutical Tablets,Quantification,Low-Frequency Raman Spectroscopy,THz-Raman,Crystalline Polymorph
更新于2025-09-23 15:23:52
-
Portable and benchtop Raman spectrometers coupled to cluster analysis to identify quinine sulfate polymorphs in solid dosage forms and antimalarial drug quantification in solution by AuNPs-SERS with MCR-ALS
摘要： This paper proposes for the first time: (a) a qualitative analytical method based on portable and benchtop backscattering Raman spectrometers coupled to hierarchical cluster analysis (HCA) and multivariate curve resolution – alternating least-squares (MCR-ALS) to identify two polymorphs of antimalarial quinine sulfate in commercial pharmaceutical tablets in their intact forms and (b) a quantitative analytical method based on gold nanoparticles (AuNPs) as active substrates for surface-enhanced Raman scattering (SERS) in combination with MCR-ALS to quantify quinine sulfate in commercial pharmaceutical tablets in solution. The pure concentration and spectral profiles recovered by MCR-ALS proved that both formulation present different polymorphs. These results also were confirmed by two clusters observed in HCA model, according to their similarities within and among the samples that provided useful information about homogeneity of different pharmaceutical manufacturing processes. AuNPs-SERS coupled to MCR-ALS was able to quantify quinine sulfate in the calibration range from 150.00 to 200.00 ng mL-1 even with strong overlapping spectral profile of background SERS signal, proving that is a powerful ultrahigh sensitivity analytical method. This reduced linearity was validated through a large calibration range from 25.00 to 175.00 μg mL-1 used in a reference analytical method based on high performance liquid chromatography with diode array detector (HPLC-DAD) coupled to MCR-ALS for analytical validation purposes even in the presence of coeluted compound. The analytical methods herein developed are fast, because second-order chromatographic data and first-order SERS spectroscopic data where obtained in less than 6 and 2 min, respectively. Concentrations of quinine sulfate were estimated with a low root mean square error of prediction (RMSEP) values and a low relative error of prediction (REP%) in the range 1.8-6.1%.
关键词： Quinine sulfate pharmaceutical tablets,Raman spectrometer,polymorphs,HCA and MCR-ALS,AuNPs-SERS
更新于2025-09-23 15:19:57