Abstract
The main purpose of the study was to evaluate various pre-processing and quantification approaches of Raman spectrum to quantify low level of amorphous content in milled lactose powder. To improve the quantification analysis, several spectral pre-processing methods were used to adjust background effects. The effects of spectral noise on the variation of determined amorphous content were also investigated theoretically by propagation of error analysis and were compared to the experimentally obtained values. Additionally, the applicability of calibration method with crystalline or amorphous domains in the estimation of amorphous content in milled lactose powder was discussed.Two straight baseline pre-processing methods gave the best and almost equal performance. By the succeeding quantification methods, PCA performed best, although the classical least square analysis (CLS) gave comparable results, while peak parameter analysis displayed to be inferior.The standard deviations of experimental determined percentage amorphous content were 0.94% and 0.25% for pure crystalline and pure amorphous samples respectively, which was very close to the standard deviation values from propagated spectral noise.The reasonable conformity between the milled samples spectra and synthesized spectra indicated representativeness of physical mixtures with crystalline or amorphous domains in the estimation of apparent amorphous content in milled lactose.
Highlights
The interest in the quantitative analysis of amorphous content of pharmaceutical solids has increased considerably the last years
Many analytical techniques may be used to quantify modest to high levels of amorphous content in a solid, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), solution calorimetry, isothermal microcalorimetry and dynamic vapour sorption
It is reported that the quantification limit of XRPD and DSC are greater than 5% (Shah et al, 2006), whereas solution calorimetry (Hogan and Buckton, 2000), isothermal calorimetry (Buckton et al, 1995) and dynamic vapour sorption (Mackin et al, 2002; Sheokand et al, 2014; Young et al, 2007) may enable the quantification of amorphous content of less than 1%
Summary
The interest in the quantitative analysis of amorphous content of pharmaceutical solids has increased considerably the last years This stems from the facts that firstly, amorphous solids may be used to solve certain formulation problems, such as low solubility of a drug, and, secondly, the processing of crystalline particles may result in, often undesired, formation of an amorphous phase (sometimes referred to as process induced disordering) that may still have an impact on physical and chemical properties of the materials and the final pharmaceutical product performance. Many analytical techniques may be used to quantify modest to high levels of amorphous content in a solid, including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), solution calorimetry, isothermal microcalorimetry and dynamic vapour sorption. It is reported that the quantification limit of XRPD and DSC are greater than 5% (Shah et al, 2006), whereas solution calorimetry (Hogan and Buckton, 2000), isothermal calorimetry (Buckton et al, 1995) and dynamic vapour sorption (Mackin et al, 2002; Sheokand et al, 2014; Young et al, 2007) may enable the quantification of amorphous content of less than 1%
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