TY - JOUR
T1 - Characterization of the pore structure of functionalized calcium carbonate tablets by terahertz time-domain spectroscopy and X-ray computed microtomography
AU - Markl, Daniel
AU - Wang, Parry
AU - Ridgway, Cathy
AU - Karttunen, Anssi Pekka
AU - Chakraborty, Mousumi
AU - Bawuah, Prince
AU - Pääkkönen, Pertti
AU - Gane, Patrick
AU - Ketolainen, Jarkko
AU - Peiponen, Kai Erik
AU - Zeitler, J. Axel
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - imaging methods
KW - mathematical models
KW - mechanical properties
KW - physical characterization
KW - refractive index
KW - solid dosage form
KW - spectroscopy
UR - http://www.scopus.com/inward/record.url?scp=85017391273&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2017.02.028
DO - 10.1016/j.xphs.2017.02.028
M3 - Article
C2 - 28267446
AN - SCOPUS:85017391273
VL - 106
SP - 1586
EP - 1595
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 6
ER -