Use of interactive mixtures to obtain mini-tablets with high dose homogeneity for paediatric drug delivery

Abstract

Mini-tablets are suitable for children since they are easy to swallow and offer dose flexibility by adjustment of the number of units. The main objective was to investigate the use of interactive mixtures as a means to obtain high dose homogeneity in mini-tablets. The effect of carrier particle properties, mixing time, mixing equipment and sample size on homogeneity was evaluated. Micronized sodium salicylate (1% w/w) was mixed with different size fractions of spray-dried and granulated mannitol. The degree of homogeneity was expressed as the relative standard deviation (RSD). Mini-tablets were prepared from the interactive mixtures and characterized with respect to uniformity of mass and content, dose homogeneity, tablet strength, wetting time and disintegration time. Generally, RSD decreased with increasing mixing times, and levelled out around 3–4%. The lowest RSD was achieved with carrier particles of intermediate sizes; 125–180 μm, 180–250 μm and 250–355 μm. The tumbling mixer was considered to be more suitable than the planetary mixer and longer mixing times were required to reach high degree of homogeneity in the smaller sample size. Mini-tablets showed high dose homogeneity as well as appropriate tensile strength and disintegration time to be suitable as orally disintegrating mini-tablets for children.