Time-Resolved Spectroscopy for Pharmaceutical Applications

Abstract: The work presented in this thesis aims at improving spectroscopic techniques for analysis of pharmaceutical solids. This improvement is achieved by the combining and development of instrumentations and data evaluation tools from two research fields: the fields of near infrared spectroscopy and biomedical optics. The thesis include the construction and evaluation of different variable selection techniques. Variable selection is an important tool used to improve the evaluation of spectroscopic data. Variable selection was applied to near infrared data from pharmaceutical tablets and mid-infrared data from atmospheric gases. A novel instrumentation, using a photonic crystal fibre for light generation and a streak camera for detection, was developed, tested and used for time-resolved measurements. The system covers a wavelength range from 500 to 1200 nm and the time-resolution was measured to be 30 ps. The system proved to be very versatile and was used both for reflectance and transmission measurements. New evaluation schemes for time-resolved data were developed. A new algorithm, based on diffusion theory was evaluated using time-resolved data required on apples. The same data was used to study the performance of a data evaluation scheme based on diffusion theory combined with least square support vector machines. Both tested evaluation schemes showed results comparable with results computed by the conventional evaluation scheme based on diffusion theory. Time-resolved measurements were conducted on pharmaceutical solids. Quantitative analysis of intact tablets using time-resolved data was superior to analysis made using conventional near infrared data, especially when the difference in physical properties between the measured samples were large. An analysis method combining time-resolved spectroscopy and conventional near infrared spectroscopy was also developed. The scheme allows evaluation over a larger wavelength range than the one covered by the time-resolved system. The maximum range is only limited to the range covered by the near infrared spectroscopic instrument. The work also takes the first step toward the construction of a bench-top system, showing that the data from a simplified time-resolved system would still give valuable results.