Comparison of Terahertz Pulse Imaging and Near-Infrared Spectroscopy for Rapid, Non-Destructive Analysis of Tablet Coating Thickness and Uniformity
In this study, coating thickness and uniformity of production-scale pharmaceutical tablets were investigated using near-infrared (NIR) and terahertz pulse imaging (TPI) spectroscopy. Two coating formulations were considered; samples for each coating formulation were obtained at 0, 1, 2, 3, 4, and 5% coating weight. NIR spectra were collected, and regressed with respect to batch percent weight gain. While standard errors of calibration (SEC) less than 0.5% were observed for both formulations, the calibrations were not specifically sensitive to coating thickness. An upper limit for NIR coating thickness analysis was estimated to be ∼4–6% weight gain for this system. The NIR calibrations were used as filters to choose subsets of samples for TPI, and as a secondary method for validation of TPI results. The features in TPS time-domain spectra result when an incident THz plane wave meets a refractive index interface, which may be converted to an absolute distance. Therefore, assuming that a discernible difference in refractive index between coating material and core exists, coating thickness can be determined non-destructively. Coating thickness measurements from TPI and NIR spectroscopy were compared to estimate the lower limit for quantitative TPI coating analysis; a lower limit of ∼35 mm was obtained for this system. Optical microscopy was employed on a subset of samples to validate absolute thickness values; reasonable correlations between the three methods were obtained. TPI was considered advantageous relative to the other methods, as similar results were obtained without the need for destructive sampling or empirical calibration development.
KeywordsTablet coating Thickness Terahertz Imaging Spectroscopy Near-infrared Chemometrics PAT
The authors would like to thank the Duquesne University department of biology for use of their microscopy facilities and equipment.
- 1.Ansel HC, Allen LV Jr, Popovich NG. Capsules and tablets. Pharmaceutical dosage forms and drug delivery systems. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. p. 179–228.Google Scholar
- 2.Cogdill RP, Anderson CA, Delgado-Lopez M, Chisholm R, Bolton R, Herkert T, et al. Process analytical technology case study, part II: development and validation of quantitative for tablet API content and hardness. AAPS PharmSciTech 2005;6(2):273–83.Google Scholar
- 3.Cogdill RP, Anderson CA, Delgado-Lopez M, Molseed D, Chisholm R, Bolton R, et al. Process analytical technology case study, part I: feasibility studies for quantitative NIR method development. AAPS PharmSciTech 2005;6(2):262–72.Google Scholar
- 4.Cogdill RP, Anderson CA, Drennen JK. Process analytical technology case study, part III: calibration monitoring and transfer. AAPS PharmSciTech 2005;6(2):284–97.Google Scholar
- 5.FDA. PAT—a framework for innovative manufacturing and quality assurance; 2004.Google Scholar
- 8.Cogdill RP, Drennen JK. Near-infrared spectroscopy. In: Brittain HG, editor. Spectroscopy of pharmaceutical solids. New York, NY: Taylor & Francis Group; 2006. p. 313–412.Google Scholar
- 15.Cogdill RP, Short SM, Forcht RN, Shi Z, Shen YC, Taday PF, et al. An efficient method development strategy for quantitative chemical imaging via terahertz pulse spectroscopy. J Pharm Innovation 2006;1(1):63–75.Google Scholar
- 16.Shen YC, Lo T, Taday PF, Cole BE, Tribe WR, Kemp MC. Detection and identification of explosives using terahertz pulsed spectroscopic imaging. Appl Phys Lett 2005;86(241116):24–31.Google Scholar
- 20.Cole BE, Woodward RM, Crawley D, Wallace VP, Arnone DD, Pepper M. Terahertz imaging and spectroscopy of human skin, in-vivo. Proc SPIE 2001;4276(1–10):1–10.Google Scholar