Technical concerns on the subdivision of multilayer tablets

Abstract

Multilayer tablets are gaining popularity for combining active pharmaceutical ingredients in a single dosage unit. However, the need to personalize drug treatment frequently demands the subdivision of such dosage forms. This study aimed to evaluate the performance of commercial multilayer tablets from different geographic origins for subdivision. An analysis of morphology, dimensions, mechanical resistance, and mass measurements of the halves after subdivision by a tablet splitter was performed, as well as an analysis of the adhesion layers. The tablets failed to meet acceptable standards for mass variation (more than 10 % in over 60 % of the samples), mass loss, and friability (more than 3.0 and 1.5 % in half of the samples, respectively). Furthermore, most of the tablets had exhibited layer separation or weakening after the subdivision, resulting in a marked decrease in fracture force to values below 10 N. Several factors, including matrix heterogeneity and high thickness, may contribute to these results. Delamination in multilayer tablets represents a significant quality issue that can compromise their therapeutic utility. Given such a scenario, the subdivision of multilayer tablets should be avoided until developers implement appropriate strategies, ensuring safe conditions for the user.