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 300 mg 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 165.18 mg vs 133.83 mg. 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.