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 degrees 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 degrees 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 degrees 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. (C) 2009 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.