Influence of Non-Water-Soluble Placebo Pellets of Different Sizes on the Characteristics of Orally Disintegrating Tablets Manufactured by Freeze-Drying

The present study describes the development of an orally disintegrating tablet containing a non-water-soluble drug delivery system. A model system was applied to evaluate the effect of different-sized particles on tablet characteristics. Cellets were incorporated into tablets prepared by freeze-drying from a 100 mg/mL mannitol or sucrose solution. Particle size distributions were 200-355 μm for Cellets 200 (C200) and 500-710 μm for Cellets 500 (C500). An examination of the tablets revealed that the particles could not be sufficiently embedded in mannitol because of its crystalline nature. The tablet hardness was also inadequate. In contrast, the hardness of sucrose tablets was increased by the addition of Cellets 500. Therefore, the sucrose-based formulation was studied further. Binders [hydroxyethylstarch, sodium alginate, methylcellulose (MC), and gelatin] were added in different concentrations, and tablets were made either with or without placebo pellets. A positive effect of the Cellets on the hardness of tablets was identified. Furthermore, disintegration time could be clearly reduced by Cellets for tablets made from 100 mg/mL sucrose with addition of 10 mg/mL MC, 20 or 40 mg/mL gelatin. The freeze-dried tablet index revealed that the formulations of sucrose with 50 mg/mL hydroxyethylstarch or 20 mg/mL gelatin were particularly advantageous.