title: Investigation of internal structure of fine granules by microtomography using synchrotron X-ray radiation.
abstract: Computed tomography (CT) using synchrotron X-ray radiation was evaluated as a non-destructive structural analysis method for fine granules. Two kinds of granules have been investigated: a bromhexine hydrochloride (BHX)-layered Celphere CP-102 granule coated with pH-sensitive polymer Kollicoat Smartseal 30-D, and a wax-matrix granule constructed from acetaminophen (APAP), dibasic calcium phosphate dehydrate, and aminoalkyl methacrylate copolymer E (AMCE) manufactured by melt granulation. The diameters of both granules were 200-300 μm. CT analysis of CP-102 granule could visualize the laminar structures of BHX and Kollicoat layers, and also visualize the high talc-content regions in the Kollicoat layer that could not be detected by scanning electron microscopy. Moreover, CT analysis using X-ray energies above the absorption edge of Br specifically enhanced the contrast in the BHX layer. As for granules manufactured by melt granulation, CT analysis revealed that they had a small inner void space due to a uniform distribution of APAP and other excipients. The distribution of AMCE revealed by CT analysis was also found to involve in the differences of drug dissolution from the granules as described previously. These observations demonstrate that CT analysis using synchrotron X-ray radiation is a powerful method for the detailed internal structure analysis of fine granules.
authors: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Shuji
authors: S
authors: Noguchi
authors: Ryusuke
authors: R
authors: Kajihara
authors: Yasunori
authors: Y
authors: Iwao
authors: Yukari
authors: Y
authors: Fujinami
authors: Yoshio
authors: Y
authors: Suzuki
authors: Yasuko
authors: Y
authors: Terada
authors: Kentaro
authors: K
authors: Uesugi
authors: Keiko
authors: K
authors: Miura
authors: Shigeru
authors: S
authors: Itai
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D001964:Bromhexine / Q000737:chemistry; D002130:Calcium Phosphates / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011728:Pyridones / Q000737:chemistry; D017356:Synchrotrons; D013627:Talc / Q000737:chemistry; D014885:Waxes / Q000737:chemistry; D055114:X-Ray Microtomography / Q000379:methods*; D014965:X-Rays
chemical_list: D002130:Calcium Phosphates; D005079:Excipients; D005989:Glycerides; D008689:Methacrylates; D011728:Pyridones; D014885:Waxes; C108010:CP 102; D013627:Talc; C048159:glyceryl monostearate; D000082:Acetaminophen; D008353:Mannitol; D002482:Cellulose; C008079:hydroxypropylcellulose; C494366:calcium phosphate, dibasic, dihydrate; D001964:Bromhexine