Detection of porosity of pharmaceutical compacts by terahertz radiation transmission and light reflection measurement techniques Prince Bawuah a, *, Alessandra Pierotic Mendia a , Pertti Silfsten a , Pertti Pääkkönen a , Tuomas Ervasti b , Jarkko Ketolainen b , J. Axel Zeitler c , Kai-Erik Peiponen a a Institute of Photonics,University of Eastern Finland, P. O. Box 111, FI-80101 Joensuu, Finland b School of Pharmacy, Promis Centre,University of Eastern Finland, P. O. Box 1617, FI-70211, Joensuu, Finland c Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom ARTICLE INFO Article history: Received 17 December 2013 Received in revised form 3 February 2014 Accepted 8 February 2014 Available online 12 February 2014 Keywords: Pharmaceutical tablets Porosity Terahertz Intrinsic refractive index Specular gloss Surface roughness ABSTRACT We report on the non-destructive quantification of the porosity of pharmaceutical compacts (microcrystalline cellulose tablets) by using both optical and terahertz techniques. For the full analysis of the porosity of pharmaceutical tablets, the results obtained in both cases have shown that optical and terahertz techniques are complementary. The intrinsic refractive index of microcrystalline cellulose was estimated using the effective refractive index obtained from the time delay of the THz pulse together with the Bruggeman model for effective media. Once this intrinsic refractive index is known, the unknown porosity of the tablet can be estimated with the aid of the measured effective refractive index as well as the thickness of the pharmaceutical tablet. The method was tested using a set of thirteen tablets having different porosities. It is shown that the error in the estimation of the unknown tablet’s porosity is less than 1%. In addition, surface roughness was measured by using an optical interferometer and gloss by using a diffractive-optical-element based glossmeter. The measurement was achieved by scanning the tablets with a probe beam and detecting the reflected light. The surface roughness and gloss data show relatively good correlation with the porosities of the tablets. ã 2014 Elsevier B.V. All rights reserved. 1. Introduction Terahertz (THz) radiation has a unique ability to excite low frequency bond vibrations, crystalline phonon vibrations, hydro- gen-bonding stretches, torsion vibrations and molecular rotations in gases (Chantry, 1971). This enables a range of interesting applications in materials characterization and the interaction of terahertz radiation with pharmaceutical tablets for the identifica- tion of pharmaceutical ingredients is one example for an emerging field of this technology (Taday, 2004; Shen, 2011). In this industry, process analytical technology (PAT) applications have been reported based on this technology: a typical example is the use of terahertz sensing for in-line monitoring of the coating thickness of pharmaceutical tablets (May et al., 2011). Recently, a number of studies have investigated the potential of terahertz spectroscopy for the characterization of pharmaceutical solids. In the realm of differentiating pharmaceutical polymor- phism and crystallinity, terahertz spectroscopic techniques have proven great sensitivity. A clear manifestation to this claim is the differentiation of benzoic acid and some monosubstituted deriv- atives, including salicylic acid and acetylsalicylic acid (aspirin) using terahertz time-domain spectroscopy (THz-TDS) (Walther et al., 2002). Just a year later, Taday et al. (2003) succeeded in using THz-TDS to clearly identify ranitidine hydrochloride crystalline forms 1 and 2. In an attempt to extend the work of Taday et al. (2003), Strachan et al. (2004) showed the applicability of the THz- TDS technique to a broad range of solid-state forms of pharmaceu- tical compounds by differentiating crystalline, amorphous and super cooled liquid crystalline forms. Although the characterization and control of all possible polymorphic forms of a new active pharmaceutical ingredient (API) are key factors for successful product development in the pharmaceutical industry, the knowledge of the microstructure, with porosity of the final product (i.e. tablets) being a significant parameter, also plays a major role since it affects the functionality of the solid dosage form. The porosity of a pharmaceutical tablet is defined as the fraction of air voids with respect to the total volume of the tablet. Porosity plays an important role in the ingress of dissolution medium (Delalonde and Ruiz, 2008), subsequent disintegration and release of the active API from the tablet * Corresponding author. Tel.: +358 466420273. E-mail address: prince.bawuah@uef.fi (P. Bawuah). http://dx.doi.org/10.1016/j.ijpharm.2014.02.011 0378-5173/ ã 2014 Elsevier B.V. All rights reserved. International Journal of Pharmaceutics 465 (2014) 70–76 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm