title: Microtomographic studies of subdivision of modified-release tablets.
abstract: The uniformity of dosage units within a certain batch is ensured when each unit contains the active pharmaceutical ingredient (API) within a narrow range around the label claim. For tablets containing a score-line authorised for dose reductions, the European Pharmacopoeia (Ph. Eur.) considers that the uniformity of the tablet parts may be based on weight measurements regardless of the tablet type (immediate or modified release). This is because it is up to the regulatory authorities first to assess whether the tablet may contain a score-line for such use. X-ray microtomography was applied to assess the symmetry of 36 modified release tablets, containing 300mg of theophylline. The sum of the volume and surface area of the pellets in the subdivided tablets were compared. Simulations were carried out to identify the optimal amount of pellets in the tablet mass. The maximum difference in the API content between two subdivided halves was 165.18mg vs 133.83mg. If the amount of pellets in the tablet mass would drop below 13% on the basis of the pellet surface area, then the Ph. Eur. requirements would be exceeded. The amount of pellets in the tablet halves resulting in the greatest variability in API content was 38%. The results of this study indicate that the pellets were not distributed uniformly in the tablet mass. Thus, the uniformity of the dose in both halves of a tablet containing pellets cannot be based on the weight measurements i.e. it is necessary to develop further standards for tablet subdivision. Microtomographic methods are a very interesting alternative to expensive and time-consuming pharmacokinetic studies.
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Department of Basic Biomedical Science, Kasztanowa Street 3, Sosnowiec 41-200, Poland. Electronic address: swilczynski@sum.edu.pl.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Wilczyński
authors.affiliation: Department of Biomedical Computer Systems, University of Silesia, Faculty of Computer Science and Materials Science, Institute of Computer Science, Będzińska Street 39, Sosnowiec 41-200, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Koprowski
authors.affiliation: Department of Biomedical Computer Systems, University of Silesia, Faculty of Computer Science and Materials Science, Institute of Computer Science, Będzińska Street 39, Sosnowiec 41-200, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Duda
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Department of Applied Pharmacy, Kasztanowa Street 3, Sosnowiec 41-200, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Banyś
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Department of Basic Biomedical Science, Kasztanowa Street 3, Sosnowiec 41-200, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Błońska-Fajfrowska
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D008297:Male; D013607:Tablets / Q000737:chemistry*; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets
keywords: Microtomography; Modified-release tablet; Pellets; Tablet splitting; Tablet uniformity