Tricalcium Citrate Tetrahydrate TB as Filler in Direct Compression of Minitablets.

Minitablets are an innovative dosage form with a diameter of ≤ 3 mm that offer solutions for many unmet needs in pediatric patient populations, as they are easy to swallow and allow for individual dosage adjustments based on current body weight. They provide a valuable alternative to often-used normal-sized tablets or liquid drug formulations, while combining palatability with improved drug product stability. However, producing minitablets via direct compression is challenging, as excipients must meet high demands to ensure excellent flowability, suitable content uniformity, rapid disintegration times and good palatability simultaneously. To address these challenges, the use of tricalcium citrate tetrahydrate (TCC TB), a brittle direct compression excipient with outstanding flow properties, excellent hardness yield and neutral taste was investigated. In this context, a direct comparison to the frequently used fillers Tablettose® 80, galenIQ™ 721, Vivapur® 102 and Vivapur® 200 was undertaken. Minitablets with a total weight of 8 mg were produced using a StylOne® Classic 105 ML compaction simulator. As model drug for pediatric use, furosemide was chosen in a drug load of 6.25% or 12.5%. Superior performance of TCC TB minitablets was found in terms of disintegration time, content uniformity and tensile strength. For galenIQ™ 721, tableting was challenging, as tablet defects occurred due to material sticking to the punches. Tablettose® 80 failed to achieve acceptable content uniformity and tensile strength values. Both Vivapur® grades achieved comparable results to TCC TB minitablets. Consequently, TCC TB presents high potential as filler for minitablet production in an extended industrial setting.