Relative Humidity Cycling: Implications on the Stability of Moisture-Sensitive Drugs in Solid Pharmaceutical Products

The stability of a moisture-sensitive drug in tablet formulations depends particularly on the environment's relative humidity (RH) and the products' prior exposure to moisture. This study was designed to understand drug stability in relation to the moisture interaction of the excipients, moisture history of the tablets, and RH of the environment. The stability study was performed on tablets containing acetylsalicylic acid (ASA), formulated with common pharmaceutical excipients like native maize starch, microcrystalline cellulose (MCC), partially pregelatinized maize starch (PGS), dicalcium phosphate dihydrate (DCP), lactose, and mannitol. The tablets were subjected to storage conditions with RH cycling alternating between 53% and 75%. Results were also compared to tablets stored at a constant RH of 53% or 75%. The excipients demonstrated marked differences in their interactions with moisture. They could be broadly grouped as excipients with RH-dependent moisture content (native maize starch, MCC, and PGS) and RH-independent moisture content (DCP, lactose, and mannitol). As each excipient interacted differently with moisture, degradation of ASA in the tablets depended on the excipients' ability to modulate the moisture availability for degradation. The lowest ASA degradation was observed in tablets formulated with low moisture content water-soluble excipients, such as lactose and mannitol. The impact of RH cycling on ASA stability was apparent in tablets containing native maize starch, MCC, PGS, or DCP. These findings suggested that the choice of excipients influences the effect of moisture history on drug stability. The results from studies investigating moisture interaction of excipients and drug stability are valuable to understanding the inter-relationship between excipients, moisture history, and drug stability.