Analysis of single particle photodegradation using photothermal infrared microspectroscopy

The increasing use of high throughput methods, coupled with the need to develop approaches to anticipate long term stability issues, has necessitated the introduction of testing approaches whereby extremely small samples may be rapidly analysed. A novel method is described whereby the UV light-induced degradation of single particles of a model drug, nifedipine, may be rapidly and simply monitored using photothermal infrared microspectroscopy (PTMS). The technique involves the contact attachment of individual particles to a heated probe tip composed of a modified Wollaston wire which enables temperature fluctuations to be measured. Application of a focused IR beam to excite the sample allows measurement and subsequent Fourier transformation of the resultant interferogram to produce an IR spectrum which is in good agreement with that obtained from conventional IR methods. By application of a UV source to the assembly for specified time periods, we demonstrate that it is possible to monitor the appearance of peaks associated with degradation products as a function of time. The technique is critically evaluated in terms of practical issues associated with volatilization, particle size effects and orientation to the light source as well as more general issues associated with the sensitivity, resolution and quantitative interpretation of data from the PTMS technique. Overall the method has been shown to be capable of rapid measurement of photo-instability on individual particles, with important implications for development of the approach as a rapid screening or high throughput technique, although there are practical and theoretical limitations to reliable quantitative analysis at the present time.