Detection of tulobuterol crystal in transdermal patches using terahertz pulsed spectroscopy and imaging.

Applicability of a Terahertz Pulsed Spectroscopy (TPS) and a Terahertz Pulsed Imaging (TPI) for detection of tulobuterol (TBR) crystals in transdermal patches was investigated. Because TBR has high permeability in dermis, crystalline TBR in patch matrices contributes to controlling the release rate of TBR from a matrix. Therefore, crystalline TBR is one of the important factors for quality control of TBR transdermal tapes. A model tape that includes 5 w/w%, 10 w/w%, 20 w/w% or 30 w/w% of TBR was measured by TPS/TPI. TBR crystals in the matrices were successfully detected by TPI. Identification of TBR in an image of a crystal-like mass was done by comparison between the spectra of tapes and a TBR standard substance. These results indicate that TPS and TPI are applicable to identifying crystalline lumps of an active drug in tapes for quality control.

Terahertz pulsed imaging of basal cell carcinoma ex vivo and in vivo.

BACKGROUND: Terahertz radiation lies between the infrared and microwave regions of the electromagnetic spectrum and can be used to excite large amplitude vibrational modes of molecules and probe the weak interactions between them. Terahertz pulsed imaging (TPI) is a noninvasive imaging technique that utilises this radiation. OBJECTIVES: To determine whether TPI could differentiate between basal cell carcinoma (BCC) and normal tissue and to test whether it can help facilitate delineation of tumour margins prior to surgery. METHODS: A portable TPI system was used in the clinic to image 18 BCCs ex vivo and five in vivo. RESULTS: The diseased tissue showed a change in terahertz properties compared with normal tissue, manifested through a broadening of the reflected terahertz pulse. Regions of disease identified in the terahertz image correlated well with histology. CONCLUSIONS: This study has confirmed the potential of TPI to identify the extent of BCC in vivo and to delineate tumour margins. Further clinical study of TPI as a surgical tool is now required.

The use of Fourier-transform infrared spectroscopy for the quantitative determination of glucose concentration in whole blood.

Fourier-transform infrared transmission spectroscopy has been used for the determination of glucose concentration in whole blood samples from 28 patients. A 4-vector partial least-squares calibration model, using the spectral range 950-1200 cm(-1), yielded a standard-error-of-prediction of 0.59 mM for an independent test set. For blood samples from a single patient, we found that the glucose concentration was proportional to the difference between the values of the second derivative spectrum at 1082 cm(-1) and 1093 cm(-1). This indicates that spectroscopy at these two specific wavenumbers alone could be used to determine the glucose concentration in blood plasma samples from a single patient, with a prediction error of 0.95 mM.

Using Terahertz pulse spectroscopy to study the crystalline structure of a drug: a case study of the polymorphs of ranitidine hydrochloride.

We describe the application of Terahertz pulse spectroscopy to polymorph identification. The particular compounds investigated were the different crystalline Forms 1 and 2 of ranitidine hydrochloride, both in the pure form and also obtained as a marketed pharmaceutical product. Identification was clear. The technique has advantages that excitation is not via a powerful laser source, as used in Raman spectroscopy, so phase changes or photochemical reactions in polymorphs do not occur. Terahertz absorption spectral interpretation and instrumentation are similar to basic Fourier transform infrared (FTIR) spectroscopy and therefore easy to understand. The sample preparation techniques used are the same as those used in FTIR and Raman spectroscopies. The data obtained is complementary to Raman Spectroscopy. As the selection rules are different between the two techniques, we are able to obtain new data set directly related to crystalline structure adding to that obtained by Raman spectroscopy. Terahertz pulse spectroscopy provides information on low-frequency intermolecular vibrational modes; these are difficult to assess in Raman spectroscopy due to the proximity of the laser exciting line. It is concluded that the method has a wide range of applications in pharmaceutical science including formulation, high throughput screening, and inspection in storage.

Terahertz pulse spectroscopy of biological materials: L-glutamic Acid.

We report the terahertzpulse spectra of L-glutamic acid. Thereare a number of well-resolved transitionsin the 1.75-2.5 THz (58-83 cm(-1))region. These are compared with publishedtheoretical data on intra andintermolecular transitions. We could notfind any correlation with the theoreticalvalues. However, it was noted that thetheoretical model did not include anycrystalline or hydrogen-bonding effects.

Determination of Glucose Concentration in Whole Blood using Fourier-Transform Infrared Spectroscopy.

Fourier-transform infrared(FTIR) transmission spectroscopy has beenused for the determination of glucoseconcentrations in whole blood samples fromtwenty-eight patients. A four-vectorpartial least squares calibration model,using the spectral range 950-1200 cm(-1),yielded a standard error of prediction of0.59 mM for an independent test set. Forblood samples from a single patient, wefound that the glucose concentration wasproportional to the difference between thevalues of the second derivative spectrum at1082 cm(-1) and 1093 cm(-1), suggestingthat these two specific wavelengths can beused for determining glucose concentrationsin blood.

Terahertz pulsed imaging of skin cancer in the time and frequency domain.

Terahertz Pulsed Imaging(TPI) is a new medical imaging modality forthe detection of epithelial cancers. Overthe last two years this technique has beenapplied to the study of in vitrobasal cell carcinoma (BCC). Usingtime-domain analysis the contrast betweendiseased and normal tissue has been shownto be statistically significant, andregions of increased terahertz (THz)absorption correlated well with thelocation of the tumour sites in histology.Understanding the source of this contrastthrough frequency-domain analysis mayfacilitate the diagnosis of skin cancer andrelated skin conditions using TPI. Wepresent the first frequency-domain analysisof basal cell carcinoma in vitro,with the raw power spectrum giving aninsight into the surface features of theskin. Further data manipulation is requiredto determine whether spectral informationcan be extrapolated at depth. These resultshighlight the complexity of working inreflection geometry.