Application of the quantitative detection of a change in concentration of magnesium stearate in a feeder tube of tableting manufacture by real-time near-infrared spectroscopy.

Process analytical technology is important for the analysis and control of manufacturing processes. Near-infrared spectroscopy is widely used in various process analytical technologies for the analysis of the chemical componentsof solid dosage forms. Lubrication is an important process carried out before a tablet is produced. In this process, the concentration of lubricant, such as magnesium stearate (StMg), might change for one of many reasons during powder transport, which would be a critical problem such as variation in tablet compressibility and dissolution failure of compressed tablets. Our group investigated the feasibility of the quantitative monitoring of a change in the concentration of StMg in the feeder tube of tableting equipment employing real-time near-infrared spectroscopy.

Strategic development of a multivariate calibration model for the uniformity testing of tablets by transmission NIR analysis.

The use of transmission near infrared spectroscopy (TNIRS) is of particular interest in the pharmaceutical industry. This is because TNIRS does not require sample preparation and can analyze several tens of tablet samples in an hour. It has the capability to measure all relevant information from a tablet, while still on the production line. However, TNIRS has a narrow spectrum range and overtone vibrations often overlap. To perform content uniformity testing in tablets by TNIRS, various properties in the tableting process need to be analyzed by a multivariate prediction model, such as a Partial Least Square Regression modeling. One issue is that typical approaches require several hundred reference samples to act as the basis of the method rather than a strategically designed method. This means that many batches are needed to prepare the reference samples; this requires time and is not cost effective. Our group investigated the concentration dependence of the calibration model with a strategic design. Consequently, we developed a more effective approach to the TNIRS calibration model than the existing methodology.

Distribution of ethenzamide and other ingredients on granule surfaces studied by Raman microspectroscopy and mapping.

Distributions of API and medical additives in granules were analyzed using Raman microspectroscopy and mapping. In order to clearly detect ingredients present at low levels, the characteristic peak for each ingredient was used for identification. Two granulation processes, tumbling granulation and high-shear granulation were selected to examine the feasibility of Raman microspectroscopy for investigating granules. Ethenzamide, lactose monohydrate, cornstarch and methylcellulose were used to make model granules. Methylcellulose was distributed homogeneously from the early stage in both granulation methods. Cornstarch and lactose showed similar distribution properties in high-shear granulation. It was presumed from this observation that similar chemical structures with high-hydrophilic groups in the two compounds determined their similar distribution properties. These results suggest that Raman microspectroscopy using the unique absorption peak of each ingredient can detect each ingredient in the individual pixel size (2 x 2 microm). This analytical method can contribute to evaluation of granular conditions and granulation processes.

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.

Chemical mapping of tulobuterol in transdermal tapes using microscopic laser Raman spectroscopy.

Microscopic Laser Raman Spectroscopy and Mapping (MLRSM) technique was used to investigate the distribution of tulobuterol (TBR) crystals in transdermal tapes. TBR is one of suitable compounds for the transdermal pharmaceuticals because it has high permeability into skin. In case of TBR transdermal tapes, some commercial products also contain TBR crystals in order to control a release rate from a matrix. Therefore, the presence of TBR crystals in the matrix is a critical factor for quality assurance of this type of TDDS tapes. The model tapes prepared here employed two kinds of matrices, i.e., rubber or acrylic, which are generally used for transdermal pharmaceuticals. TBR crystals in the matrix were observed by MLRSM. Accurate observation of the distribution of TBR in the tapes was achieved by creating a Raman chemical map based on detecting unique TBR peak in each pixel. Moreover, differences in the growth of TBR crystals in the two kinds of matrices were detected by microscopic observation. MLRSM also enabled the detection of TBR crystals in commercial products. The present findings suggest that Raman micro-spectroscopic analysis would be very useful for verifying and/or assessing the quality of transdermal pharmaceuticals in development, as well as for manufacturing process control.