Application of FTIR imaging and spectroscopy to solid dosage formulations.

MUTHUDOSS, Prakash. (2011). Application of FTIR imaging and spectroscopy to solid dosage formulations. Doctoral, Sheffield Hallam University (United Kingdom)..

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The preparation of solid dispersions, in this study felodipine/polyvinyl pyrrolidone solid dispersion, is a multifaceted phenomenon. In order to understand the formation of solid dispersions two different mixed solvent system, three different temperatures and different drug loadings were selected and monitored in real time using Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy. 50 mul of the prepared solution was placed onto a pre-heated ATR crystal. The effect of PVP/API ratio, molecular interactions and effect of temperature (30°C, 40°C and 50°C) on the rate of film formation (solid dispersions) was evaluated. The changes in the peak positions, peak intensities and peak width as a function of time was monitored. The data were then analysed using peak height measurements, statistical and chemometric data analytical tools. It was shown that the nature of the solvent, the working temperature, presence of polymer and low drug loading was found to influence the rate of evaporation of solvent, molecular interactions and quality of the final product. Moreover, using thermogravimetric techniques it was complemented that the residual solvent within the systems was within the studied limits. The spatial arrangement or distribution of components within solid dispersion was found to influence the physical stability, phase behaviour, dissolution and bioavailability. Mid infrared spectroscopic imaging has been shown to be useful and has provided unique insights in to various fields. However, it has very limited applications in analysing the pharmaceutical materials. This work aims to evaluate various image processing tools in extracting process related information. Three model systems with varying chemical composition were selected. The chemical images from the regions of interest were collected using a Varian 620 FTIR Imaging instrument equipped with 64 x 64 MCT-Focal Plane Array (FPA) detector. Firstly we showed the impact of optical artefacts on the quality of the acquired image. The data was then pre-processed to remove baseline effects, pathlength variations and image processed to extract distribution maps. Agreement between the data generated using peak height measurements, compare correlation, principal component analysis and multivariate curve resolution was obtained only with the simple systems, the advantage with the latter being that the supervised and unsupervised chemometric approaches do not require any prior information about the sample and does not suffer from any physical or chemical interferences. The success of MCR-ALS over compare correlation and PCA methods is that it does not require any pure materials library and provides chemical information respectively. Moreover, implementation and data extraction is easy using MCR-ALS. It was then showed that once the optical artefacts are separated and chemically significant information is extracted, the benefits of infrared imaging was multitude. The optimised procedures were then applied to other samples to expand the applications of mid infrared imaging. There is no established paper to date describing the application of FTIR imaging to study the solvent induced phase separation in solid dispersions. One of the aims of this work is to study the impact of two different solvents on the phase behaviour of felodipine/polyvinyl pyrrolidone solid dispersions cast from different binary solvent systems. The temperature induced phase separation and degradation have been studied using differential scanning calorimetry, scanning electron microscopy, thermogravimetric etc, however we have shown the application of FTIR imaging in assessing the temperature induced degradation complemented and supported by in situ ATR-FTIR spectroscopy and thermogravimetric analysis.

Item Type: Thesis (Doctoral)
Additional Information: Thesis (Ph.D.)--Sheffield Hallam University (United Kingdom), 2011.
Research Institute, Centre or Group: Sheffield Hallam Doctoral Theses
Depositing User: EPrints Services
Date Deposited: 10 Apr 2018 17:21
Last Modified: 10 Apr 2018 17:21

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