Skip to main content
Login | Suomeksi | På svenska | In English

Browsing by Subject "Raman spectroscopy"

Sort by: Order: Results:

  • Myllymäki, Pilvi (2018)
    The majority of potential new chemical entities reaching drug development phase belong to Class II the Biopharmaceutics Classification System (BCS) which complicates formulation of orally administered drugs. Therefore, there is a need to develop methods to increase the solubility and dissolution rate. Transformation of a crystalline drug into its amorphous form can be used to enhance these properties of poorly water-soluble drugs. However, amorphous drugs are thermodynamically unstable and tend to recrystallize back to the crystalline form. Coamorphous forms are a new and promising method to stabilize amorphous form. A relatively new approach is to combine the active drug compound with an amino acid to form a coamorphous system. In this study, co-amorphous systems were prepared from gamma, alpha or amorphous form of indomethacin (IND) and tryptophan (TRP) by ball milling. The solid-state changes during milling were investigated to obtain information about the co-amorphization process. The main objective was to investigate the effects of initial solid state of indomethacin on the formation pathways. In addition, different analytical methods were compared with respect to observed endpoints of the formation process. Raman spectroscopy has not been used in previous studies regarding solid state changes in co-amorphous forms. The presence of fluorescence in amorphous systems may have limited use of the method. A time-gated Raman setup together with X-ray powder diffraction and differential scanning calorimetry (DSC) was used to investigate this kind of potentially fluorescent system. Principal component analysis of spectral data revealed that the three different binary systems had individual and direct pathways towards the same end points during milling. This indicates that the co-amorphous form formed after 60 minutes of ball milling is not dependent on the initial solid-state form of IND. Straight pathways also indicated direct transformation to the coamorphous form. DSC was found to be the most sensitive method to detect changes for the longest period during co-amorphization. Conventional Raman spectroscopy was found to be suitable for investigation of the co-amorphization process. However, time-gated Raman spectroscopy did not show significant advantages compared to conventional Raman data. This study revealed that the most stable form of IND could be used for production of co-amorphous form together with TRP. Raman spectroscopy could potentially be used for investigating coamorphization also as an in-process analytical method.
  • Heikura, Veera (2023)
    Solids most commonly come in two broad forms: crystalline or amorphous. Crystalline solids have a regular, organized long-range structure of atoms and crystals, and are characterized by having a distinct shape, specific volume, and melting point. They can also have multiple polymorphs. On the other hand, amorphous solids do not usually have a regular long-range atomic and crystal structure and their molecules are more easily separated, which makes them more soluble in their surroundings compared to crystalline solids. However, despite this, short-range order can also occur. To improve the solubility of crystalline solids, co-amorphous systems can be created by mixing together two or more chemically different compounds in a way that they don't form a regular crystalline structure, but rather an irregular, amorphous one. Co-amorphous systems can be analyzed qualitatively or quantitatively. Qualitative analysis is often the main focus when studying amorphous matter, as it can be difficult to accurately quantify these materials using techniques based on crystal structures. Additionally, many amorphous systems are made up of complex mixtures of polymers with different chemical and physical properties. This study aimed to determine the most effective method for obtaining quantitative information about the co-amorphization of indomethacin and tryptophan. Three analytical techniques were used for this purpose: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Raman spectroscopy. The co-amorphous system was created by mixing together α-indomethacin and tryptophan, γ-indomethacin and tryptophan, and amorphous indomethacin and tryptophan. This study showed that DSC, XRPD, and Raman spectroscopy are effective in providing quantitative information about crystallinity and crystal size. These techniques were able to accurately detect and characterize discrete residual crystals, and were able to measure and quantify the amount of these substances. Even though these methods may not be able to detect nanoscale structures with precision, they still provided valuable information about the crystalline and amorphous nature of the samples studied. Additionally, the fact that similar quantitative results were obtained using different analysis methods further supports the reliability of these techniques. Of all the techniques discussed, Raman spectroscopy was able to identify even small residual crystals, resulting in the highest calculated crystallinity percentage.
  • Monola, Julia (2022)
    Native nanofibrillated cellulose is wood-derived, animal-free biocompatible biomaterial which has proved the suitability of nanoscale cellulose fiber based hydrogels for 3D cell culturing and wound healing applications. The problem of freeze-drying nanofibrillated cellulose hydrogel (NFCh) has been the aggregation of the hydrophilic fibrils of the NFC during freeze-drying, which leads deformed freeze-dried cake and unsuccessful reconstitution of the sample. Molecular Dynamic (MD) simulations have been earlier applied in formulation design of NFCh for freeze-drying successfully by screening excipients based on their attraction to the surface of NFCh. The weakness of MD simulations is it can only model the fresh formulation system intend to freeze-dry, but not the actual freeze-drying process and the effect of it and the excipients to the material. To evaluate the protecting properties of excipients and therefore the accuracy of the MD simulations detailed information about changes in the physical state and molecular orientation of the formulation before and after freeze-drying is needed. Non-invasive and label-free Raman spectroscopy can be used to determine vibrational modes of molecules to investigate changes in molecular orientation of the material. The aim of this study was to investigate the possible molecular changes induced by freeze-drying of NFCh-based formulations utilizing Raman spectroscopy and evaluate the connection of the results to MD simulations. NFCh with different excipients was freeze-dried and physicochemical properties, rheology and Raman signal were measured before and after freeze-drying and compared to the literature of MD simulations. The principal component analysis (PCA) was done to the Raman spectra and differences evaluated. The spectra of all formulations differed before and after freeze-drying, and more detailed analysis was done to two most potential 0.8% NFCh based formulations, lactose 300 mM and lactose 250 mM + glycine 50 mM. They had great attraction to NFCh in MD simulations and very similar rheological properties before and after freeze-drying and reconstitution. The spectra of different state of both formulations different on areas between 400 - 500 cm-1 and 850 - 900 cm-1 based on PCA analysis contributing the mutarotation of lactose during freeze-drying and reconstitution. Freeze-drying and the absence of water molecules in NFCh formulation favor different ratios of β and α anomers than the fresh hydrated state which could be detected utilizing Raman spectroscopy. Therefore, Raman spectroscopy was confirmed to be a sensitive option to assess subtle changes in molecular orientation in fresh, freeze-dried, and reconstituted NFCh-based formulations, resulting in a detail knowledge of the molecular behavior of excipients which could be applied in MD simulations and design of better freeze-drying formulations in future.