A comparison of trehalose dihydrate and mannitol as stabilizing agents for dicalcium phosphate dihydrate based tablets.

摘要

This study investigated the possible utility of trehalose dihydrate (TD) as a tablet stabilizing agent. Acetylsalicylic acid was used as the model hydrolyzable drug and dicalcium phosphate dihydrate (DCPD) as the base excipient, because it is well documented that ASA/DCPD tablets are unstable during storage at low temperature and high relative humidity; DCPD is usually combined with mannitol in order to improve tablet stability. Tablets comprising DCPD, 10% ASA, and 0%, 10%, or 20% w/w of TD were prepared by direct compression and stored at 35 degrees C and 82.9% relative humidity for 6 months. Additionally, control tablets with DCPD and ASA, only, or with DCPD, ASA and 20% mannitol, were also evaluated. At predetermined time intervals, formulations were tested for drug content, mechanical, microstructural, and drug dissolution properties. Additionally, thermal analyses and ASA solution stability studies were carried out. Results reveal that both TD and mannitol significantly reduce degradation of ASA included in DCPD-based tablets, but neither effectively protects against the marked decline in tablet mechanical properties on aging. The ASA stabilization effects of TD and mannitol were also observed in solution, indicating an interaction between these sugars and ASA.