Non-contact weight measurement of flat-faced pharmaceutical tablets using terahertz transmission pulse delay measurements.

By measuring the time delay of a terahertz pulse traversing a tablet, and hence its effective refractive index, it is possible to non-invasively and non-destructively detect the weight of tablets made of microcrystalline cellulose (MCC). Two sets of MCC tablets were used in the study: Set A (training set) consisted of 13 tablets with nominally constant height but varying porosities, whereas Set B (test set) comprised of 21 tablets with nominally constant porosity but different heights. A linear correlation between the estimated absolute weight based on the terahertz measurement and the measured weight of both sets of MCC tablets was found. In addition, it was possible to estimate the height of the tablets by utilizing the estimated absolute weight and calculating the relative change of height of each tablet with respect to an ideal tablet. A good agreement between the experimental and the calculated results was found highlighting the potential of this technique for in-line sensing of the weight, porosity and the relative change in height of the tablets compared to a reference/ideal tablet. In this context, we propose a quantitative quality control method to assess the deviations in porosity of tablets immediately after compaction.

[1]  Yaochun Shen,et al.  Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging. , 2007, Journal of pharmaceutical sciences.

[2]  Yaochun Shen,et al.  Industrial Applications of Terahertz Imaging , 2012 .

[3]  James K Drennen,et al.  Density mapping and chemical component calibration development of four-component compacts via terahertz pulsed imaging. , 2008, Journal of pharmaceutical and biomedical analysis.

[4]  Yaochun Shen,et al.  Terahertz pulsed spectroscopy and imaging for pharmaceutical applications: a review. , 2011, International journal of pharmaceutics.

[5]  M. Luukkala,et al.  Photoacoustic evaluation of elasticity and integrity of pharmaceutical tablets , 1995 .

[6]  C. Otani,et al.  Terahertz-wave sources and imaging applications , 2006 .

[7]  Kai-Erik Peiponen,et al.  Terahertz spectroscopy and imaging , 2013 .

[8]  R. Silvennoinen,et al.  Local and average gloss from flat-faced sodium chloride tablets , 2006, AAPS PharmSciTech.

[9]  K. Fukunaga,et al.  Wiener Bounds for Complex Permittivity in Terahertz Spectroscopy: Case Study of Two-Phase Pharmaceutical Tablets , 2010, Applied spectroscopy.

[10]  Peter Kleinebudde,et al.  Evaluation of critical process parameters for intra-tablet coating uniformity using terahertz pulsed imaging. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[11]  T. Ruiz,et al.  Dissolution of pharmaceutical tablets: The influence of penetration and drainage of interstitial fluids , 2008 .

[12]  Lawrence X. Yu Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control , 2008, Pharmaceutical Research.

[13]  Peter Kleinebudde,et al.  Validation of Terahertz coating thickness measurements using X-ray microtomography. , 2012, Molecular pharmaceutics.

[14]  Kai-Erik Peiponen,et al.  A Study on the Resolution of a Terahertz Spectrometer for the Assessment of the Porosity of Pharmaceutical Tablets , 2012, Applied spectroscopy.

[15]  J. Zeitler,et al.  Using modified Kramers-Kronig relations to test transmission spectra of porous media in THz-TDS. , 2010, Optics letters.

[16]  O. Antikainen,et al.  Determination of the crushing strength of intact tablets using Raman spectroscopy. , 2008, International journal of pharmaceutics.

[17]  Clive G. Wilson,et al.  Controlled Release in Oral Drug Delivery , 2011 .

[18]  J. Zeitler,et al.  Accurate determination of optical coefficients from chemical samples using terahertz time-domain spectroscopy and effective medium theory. , 2009, Optics letters.

[19]  Xiaorong He Integration of Physical, Chemical, Mechanical, and Biopharmaceutical Properties in Solid Oral Dosage Form Development , 2009 .

[20]  Bruno C. Hancock,et al.  The relationship between the particle properties, mechanical behavior, and surface roughness of some pharmaceutical excipient compacts , 2003 .

[21]  Tuukka Prykäri,et al.  Optical and terahertz measurement techniques for flat-faced pharmaceutical tablets: a case study of gloss, surface roughness and bulk properties of starch acetate tablets , 2008 .

[22]  Lianghao Han,et al.  Hardness and density distributions of pharmaceutical tablets measured by terahertz pulsed imaging. , 2013, Journal of pharmaceutical sciences.

[23]  Kai-Erik Peiponen,et al.  Detection of porosity of pharmaceutical compacts by terahertz radiation transmission and light reflection measurement techniques. , 2014, International journal of pharmaceutics.