[Show abstract][Hide abstract]ABSTRACT: Optical coherence tomography (OCT) and terahertz pulsed imaging (TPI) are two powerful techniques allowing high quality cross-sectional images from within scattering media to be obtained non-destructively. In this paper, we report experimental results of using OCT and TPI for quantitatively characterizing pharmaceutical tablet coatings in the thickness range of 10-140 mu m. We found that the spectral OCT system developed in-house has an axial resolution of 0.9 mu m, and is capable of quantifying very thin coatings in the range of 10-60 mu m. The upper limit of 60 mu m within the tablet coating and core is owed to the strong scattering of OCT light, which has relatively short wavelengths in the range of 0.5-1.0 mu m. On the other hand, TPI utilizes terahertz radiation that has substantially long wavelengths in the range of hundreds of microns, and thus is less prone to the scattering problem. Consequently TPI has been demonstrated to be able to quantify thicker coatings in the range of 40-140 mu m and beyond. We concluded that OCT and TPI are two complementary analytical techniques for non-destructive and quantitative characterization of pharmaceutical tablet coatings. (C) 2010 Elsevier Ltd. All rights reserved.
Full-text · Article · Mar 2011 · Optics and Lasers in Engineering
[Show abstract][Hide abstract]ABSTRACT: Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by dissolution testing. Mean dissolution times (MDT) from conventional dissolution testing were correlated with terahertz waveforms, which yielded a multivariate, partial least squares regression (PLS) model with an R(2) of 0.92 for the calibration set and 0.91 for the validation set. This two-component, PLS model was built from batch I that was coated in the same environmental conditions (air temperature, humidity, etc.) to that of batch II but at different environmental conditions from batch III. The MDTs of batch II was predicted in a nondestructive manner with the developed PLS model and the accuracy of the predicted values were subsequently validated with conventional dissolution testing and found to be in good agreement. The terahertz PLS model was also shown to be sensitive to changes in the coating conditions, successfully identifying the larger coating variability in batch III. In this study, we demonstrated that TPI in conjunction with PLS analysis could be employed to assist with film coating process understanding and provide predictions on drug dissolution.
Full-text · Article · Dec 2009 · Journal of Pharmaceutical Sciences
[Show abstract][Hide abstract]ABSTRACT: Terahertz pulsed imaging (TPI) and optical coherence tomography (OCT) are two powerful techniques allowing high quality three-dimensional images from within scattering media to be obtained noninvasively. In this paper, we report experimental results of using TPI and OCT for characterizing layered samples including pharmaceutical coatings. We found that infrared OCT provides better axial resolutions whilst TPI is less prone to scattering problems thus is well suited for characterizing pharmaceutical tablet coatings.
[Show abstract][Hide abstract]ABSTRACT: Film coating thickness and terahertz electric field peak strength (TEFPS) were determined using terahertz pulsed imaging (TPI) and employed for the analysis of sustained-release coated pellets (theophylline layered sugar cores coated with Kollicoat SR:Kollicoat IR polymer blends). The effects of coating thickness, drug layer uniformity and optional curing were investigated using eight batches of pellets. Ten pellets from each batch were imaged with TPI to analyse the coating morphology (depicted in TEFPS) and thickness prior to release measurements. The results showed TEFPS values of 15.8% and 14.5% for pellets with a smooth drug layer coated at 8.2 and 12.5% (w/w) polymer weight-gain, respectively. Whereas 6.7% was derived for pellets with a coarse drug layer coated at both weight-gains. Although there were major differences in TEFPS, the resulting drug release kinetics were very similar. It was also shown that a 36 microm coating thickness difference was not drug release rate determining. These results suggested that drug release for the pellets studied was not predominately governed by drug diffusion through the polymeric film coating but probably to a large extent limited by drug solubility. TPI proved to be highly suitable to detect non-homogeneities in the drug layer and polymeric film coating.
Full-text · Article · Sep 2009 · International Journal of Pharmaceutics
[Show abstract][Hide abstract]ABSTRACT: During the process development of coated tablets, knowledge on the formation and the location of film coating 'weak spots' is a key factor to the success of the process and the resulting product batch. It is understood that the performance of the product batch may be greatly limited, and often compromised, by weak spots on the tablet film coat. This study uses circular, biconvex tablets to investigate the ability of terahertz pulsed imaging (TPI) to identify the affected areas on the tablet film coat that are critical for dissolution performance. From the TPI analysis we determined that the tablet central band exhibited the thinnest film coating, lowest coating density and highest surface roughness and thus was the performance limiting area of the film coating. Dissolution tests confirmed that the film coating on the tablet central band was indeed dissolution rate determining, with a faster mean dissolution time (MDT) of 7.4 h in comparison to 10.4 h for the convex top/bottom surface. TPI, as a nondestructive analytical technique, showed potential to be employed as a process analytical tool to probe film coating weak spots during film coating development and to assess the effect on the subsequent dissolution performance.
[Show abstract][Hide abstract]ABSTRACT: The ability of terahertz pulsed imaging (TPI) to be employed as an analytical tool for monitoring a film coating unit operation and to assess the success of a subsequent process scale-up was explored in this study. As part of a process scale-up development, a total of 190 sustained-release tablets were sampled at 10% increments of the amount of polymer applied, from a lab-scale and a pilot-scale coating run. These tablets were subjected to TPI analysis, followed by dissolution testing. Information on tablet film coating layer thickness and variations in coating density were extracted using TPI. It was found that both terahertz parameters were more sensitive and informative to product quality when compared with measuring the amount of polymer applied. For monitoring the film coating unit operation, coating layer thickness showed a strong influence on the dissolution behaviour for both the lab-scale and the pilot-scale batches. An R(2) of 0.89, root mean square error (RMSE)=0.22 h (MDT range=3.21-5.48 h) and an R(2) of 0.92, RMSE=0.23 h (MDT range=5.43-8.12 h) were derived from the lab-scale and pilot-scale, respectively. The scale-up process led to significant changes in MDT between the lab-scale and pilot-scale. These changes in MDT could be explained by the differences observed in the film coating density on samples with similar amount of polymer applied between the lab and the pilot-scale. Overall, TPI demonstrated potential to be employed as an analytical tool to help refine the coating unit operation and the scale-up procedure.
Full-text · Article · Jan 2009 · European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
[Show abstract][Hide abstract]ABSTRACT: The potential of terahertz pulsed imaging (TPI) to predict the dissolution performance in sustained-release tablets was investigated in this study. Batches of coated tablets with similar weight gain during the coating process at the lab and pilot scales were subjected to non-destructive imaging by TPI and subsequently analysed by dissolution testing. The results from the dissolution tests revealed significant differences in the product performance between the lab and pilot scales (Student t-test, P<0.05). The model-independent dissolution parameters in the pilot scale showed a prolonged mean dissolution time. This indicated that the pharmaceutical active ingredient was released at a slower rate in the pilot compared to the lab scale. While weight gain measurements (the traditional coating quality parameter), failed to provide an early indication of the product functional performance; terahertz parameters (terahertz electric field peak strength and coating layer thickness) provided insight into the subsequent dissolution behaviour. Correlations between terahertz parameters and dissolution were much stronger than correlations between weight gain and dissolution; with the R(2) value for terahertz correlations typically around 0.84 as opposed to 0.07 for weight gain correlations. This study presents the initial finding of correlations between terahertz parameters for assessing the coating quality to the dissolution performance of the coated tablet. The contributing factors for these particular correlations are also discussed.
[Show abstract][Hide abstract]ABSTRACT: The propensity of molecules to form polymorphs increases with increasing functionality. Each polymorph is a separate patentable entity and may have different therapeutic properties. It is therefore important to develop methods for the identification and quantification of polymorphs alone and within active pharmaceutical ingredients. Various vibrational spectroscopic techniques have had promising results in the quantification of polymorphs in binary mixtures. Ranitidine hydrochloride exists as two polymorphs and has been used as a test compound in the assessment of various quantification techniques (e.g. X-ray powder diffraction, Raman spectroscopy, diffuse reflectance infra-red Fourier transform spectroscopy). This study investigates the accuracy of near-infrared spectroscopy when quantifying polymorphic binary mixtures of ranitidine hydrochloride. Ranitidine hydrochloride polymorphs may be identified and quantified from near-infrared spectra; however, not to the level of accuracy displayed by Raman spectroscopy. (C) 2006 Elsevier B.V All rights reserved.
Full-text · Article · Aug 2006 · Vibrational Spectroscopy