title: Characterization of the Pore Structure of Functionalized Calcium Carbonate Tablets by Terahertz Time-Domain Spectroscopy and X-Ray Computed Microtomography.
abstract: Novel excipients are entering the market to enhance the bioavailability of drug particles by having a high porosity and, thus, providing a rapid liquid uptake and disintegration to accelerate subsequent drug dissolution. One example of such a novel excipient is functionalized calcium carbonate, which enables the manufacture of compacts with a bimodal pore size distribution consisting of larger interparticle and fine intraparticle pores. Five sets of functionalized calcium carbonate tablets with a target porosity of 45%-65% were prepared in 5% steps and characterized using terahertz time-domain spectroscopy and X-ray computed microtomography. Terahertz time-domain spectroscopy was used to derive the porosity using effective medium approximations, that is, the traditional and an anisotropic Bruggeman model. The anisotropic Bruggeman model yields the better correlation with the nominal porosity (R2= 0.995) and it provided additional information about the shape and orientation of the pores within the powder compact. The spheroidal (ellipsoids of revolution) shaped pores have a preferred orientation perpendicular to the compaction direction causing an anisotropic behavior of the dielectric porous medium. The results from X-ray computed microtomography confirmed the nonspherical shape and the orientation of the pores, and it further revealed that the anisotropic behavior is mainly caused by the interparticle pores. The information from both techniques provides a detailed insight into the pore structure of pharmaceutical tablets. This is of great interest to study the impact of tablet microstructure on the disintegration and dissolution performance.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Markl
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
authors.forename: Parry
authors.initials: P
authors.lastname: Wang
authors.affiliation: Omya International AG, Oftringen, Switzerland.
authors.forename: Cathy
authors.initials: C
authors.lastname: Ridgway
authors.affiliation: School of Pharmacy, Promis Centre, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anssi-Pekka
authors.initials: AP
authors.lastname: Karttunen
authors.affiliation: Institute of Photonics, University of Eastern Finland, Joensuu, Finland.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Chakraborty
authors.affiliation: Institute of Photonics, University of Eastern Finland, Joensuu, Finland.
authors.forename: Prince
authors.initials: P
authors.lastname: Bawuah
authors.affiliation: Institute of Photonics, University of Eastern Finland, Joensuu, Finland.
authors.forename: Pertti
authors.initials: P
authors.lastname: Pääkkönen
authors.affiliation: Omya International AG, Oftringen, Switzerland; Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Aalto, Helsinki, Finland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gane
authors.affiliation: School of Pharmacy, Promis Centre, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Ketolainen
authors.affiliation: Institute of Photonics, University of Eastern Finland, Joensuu, Finland.
authors.forename: Kai-Erik
authors.initials: KE
authors.lastname: Peiponen
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK. Electronic address: jaz22@cam.ac.uk.
authors.forename: J Axel
authors.initials: JA
authors.lastname: Zeitler
mesh_terms: D016880:Anisotropy; D002119:Calcium Carbonate / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D016062:Porosity; D011208:Powders; D012995:Solubility; D013607:Tablets; D055068:Terahertz Spectroscopy; D055114:X-Ray Microtomography
chemical_list: D005079:Excipients; D011208:Powders; D013607:Tablets; D002119:Calcium Carbonate
keywords: imaging methods; mathematical models; mechanical properties; physical characterization; refractive index; solid dosage form; spectroscopy