Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

Abstract

Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1658–1667, 2015

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

“…Of these two batches B01 disintegrated even quicker than B02 given the lower breaking force and thus larger tablet porosity. This behaviour is in good agreement with the fact that fast absorption of a fluid was observed for powder compacts that exhibit a high porosity [23, 24]. While fast fluid penetration does not directly result in the building up of the pressure, which is necessary to break the interparticulate bonds, it is a prerequisite to initiate other mechanisms like swelling of the disintegrant [25, 26].…”

A Review of Disintegration Mechanisms and Measurement Techniques

“…These key characteristics that describe the pore network structure can often be extracted sufficiently well from high-resolution three-dimensional X-ray computed microtomography (XμCT) images of porous media [76, 77], although the detectable pore sizes are often limited by the pixel size of the image and samples have to be taken from the dosage form to achieve the highest resolution (> 0.5 μm for the most commonly used commercial bench-top instruments) [78]. In addition, traditional porosimetry techniques can be employed to measure the porosity directly using liquid or gas intrusion [79, 80].…”

“…This principle enables the monitoring of the swelling and the liquid ingress as shown in Fig. 12 [77]. Yassin et al [77] demonstrated that using this technique it is possible to analyse liquid ingress and tablet swelling quantitatively.…”

“…12 [77]. Yassin et al [77] demonstrated that using this technique it is possible to analyse liquid ingress and tablet swelling quantitatively. In addition, it is possible to detect cracks that can form in some matrices due to the strain exerted by the hydration.…”

Terahertz Pulse Detection Techniques and Imaging Applications

“…(ix) Tablet dissolution is crucial in medication and is strongly afected by swelling and solvent penetration into its matrix. A relection mode TPI is used to measure swelling and solvent ingress in pharmaceutical compacts [80]. (x) Layer separation is a crucial defect in many bilayer tablets.…”