Drug solid-state screening
Rapid and precise deciphering of complex formulations
In-depth analysis of solid-state properties
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Identification of crystalline forms in ultra-low content formulations In the original tablets, the API content is low, at only 0.5%. Literature reports indicate three crystalline forms (A, B, and E) of this API (see Figure 1), with crystalline form E being particularly challenging to prepare. Upon comparing the X-ray powder diffraction patterns of the original tablets with those of the three crystalline forms reported in the literature, no corresponding diffraction peaks were found. Further comparison of the X-ray powder diffraction pattern of the original tablets with that of the main excipient, lactose monohydrate, revealed nearly identical patterns (see Figure 2). This indicates that the crystalline state of the main excipient, lactose monohydrate, severely interferes with the X-ray diffraction signals of the API in the formulation. Identification and quantification of amorphous forms Using Raman spectroscopy, single-point Raman spectra of the original formulation were acquired, as shown in Figure 3. Due to the small laser spot size (0.1 μm), each spectrum collected represents a small sample area, minimizing the influence of excipients and providing a relatively pure API spectrum. This allows differentiation from other components' signals. By matching the Raman characteristic peaks between different crystalline forms, the API crystalline form in the formulation was identified. As depicted in Figure 4, the single-point Raman spectrum collected from the original formulation represents a relatively pure API spectrum, unaffected by lactose monohydrate interference. Moreover, crystalline forms A and B exhibit distinct Raman characteristic peaks. Comparing the Raman spectra of the API in the formulation with those of crystalline forms A and B (Figure 5), it is evident that the API in the original formulation is crystalline form A. In summary, Raman spectroscopy provides a solution for crystalline analysis in the original formulation, particularly for amorphous APIs and formulations with low content, under complex conditions. The physical properties of amorphous drug structures differ significantly from crystalline forms, which can greatly impact product stability, compatibility, dissolution rate, hygroscopicity, and solvent adsorption tendencies. Furthermore, specific processing and storage conditions are crucial for products containing amorphous forms. Whether in a single compound or a formulation, mature drug development processes must include detection and quantification of low-content amorphous drug components. To accurately quantify amorphous components in drugs, we first select detection techniques tailored to specific amorphous substances, including both traditional and innovative methods. We then employ appropriate data analysis methods, such as multivariate analysis, to ensure accurate results. There are various qualitative and quantitative methods for amorphous characterization. Typically, Raman spectroscopy reveals distinct differences between the spectra of different solid-state forms of APIs. Compared to crystalline forms, Raman spectra of amorphous APIs often exhibit broader peaks and wavenumber shifts. Reference: Tian F, Zimmermann A, McGoverin C, et al. Application of Raman spectroscopy in pharmaceutical reverse engineering. Pharmaceutical Progress. 2016;12:897-905. Figure 1.X-ray diffraction patterns of API crystalline forms A, B, and E as reported in the literature Figure2.X-ray diffraction patterns of the original formulation and lactose monohydrate Figure3.Raman spectrum of lactose monohydrate in the original formulation Figure4.Raman spectrum of API in the original formulation Raman spectra of crystalline forms A and B from the literature (A: Crystalline form A; B: Crystalline form B; C: Tablet containing API; P: Blank excipient) Our company can identify the crystalline form of active pharmaceutical ingredients (APIs) in semi-solid formulations with API content as low as 0.05%. |
Improving drug absorption through solid-state technology is the foundation of all innovative technologies at Xinyang Weikang.
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