Improved chemical stability of ascorbic acid and thiamine nitrate in L-HPC granules

Abstract

The stability of drugs in extruded granules prepared with low substituted hydroxypropylcellulose (L-HPC) and water was investigated using ascorbic acid (AA) and thiamine nitrate (TN) as model drugs. d-Mannitol was used as the control additive for a comparison with L-HPC. The percentage of AA remaining after storage at 60 °C for 14 days in a closed glass bottle was 57% in d-mannitol granules and 89% in L-HPC granules, showing higher stability of AA in L-HPC granules. On powder X-ray diffraction measurement, AA in L-HPC and d-mannitol granules was in an amorphous state. The loss on drying (LOD) (1 g, 105 °C, 2 h) of the granules containing both AA and TN was higher in L-HPC granules (1.96%). The moisture content around AA and TN in granules was calculated. The contents were 1.36% and 4.67% in L-HPC and d-mannitol granules, respectively. Furthermore, the water activities at 25–40 °C were measured in L-HPC and d-mannitol granules, being lower in L-HPC granules at all measurement temperatures. These findings suggested that the superior storage stability of AA in granules prepared with L-HPC was due to L-HPC-induced reduction of the moisture content around AA and TN and water activity of the granules.