Overcoming formulation challenges of a moisture-sensitive API using Tricalcium citrate TB and anhydrous Trimagnesium citrate in direct compression.

Moisture-sensitive active pharmaceutical ingredients (API) pose a special challenge in formulation development, as they are prone to degradation, which compromises their efficacy and patient safety. Especially the use of disintegrants in tablet formulations can compromise the stability of APIs due to their water-attracting nature. Due to its limited amount of unbound water and excellent disintegration properties, we investigated the use of tricalcium citrate tetrahydrate (TCC TB) in combination with anhydrous trimagnesium citrate (TMC) as a desiccant, as an alternative filler for a direct compression formulation of a moisture-sensitive API. Enalapril maleate (EM) was chosen as a model drug, as it degrades rapidly when mixed with moisture-containing excipients, disintegrants or water. Small-scale tablet production was conducted using various comparative fillers like spray-dried lactose monohydrate (FlowLac®90), microcrystalline cellulose (Vivapur®102) and co-processed spray-dried lactose with corn starch (StarLac®) on a compaction simulator. These tablets were investigated in a 4-week stability study under "closed-container" conditions. Further, we confirmed the scalability of the most promising direct tableting formulations to a rotary press. Our research demonstrated that using TCC TB in combination with TMC yields outstanding results regarding powder flowability, tablet tensile strength while also maintaining a rapid disintegration and ensuring superior formulation stability.