Hydrodynamic flows around tablets in different pharmacopeial dissolution tests.

We investigated the hydrodynamic flows around tablets during several pharmacopeial dissolution tests: the rotating basket (RB), paddle (PD), flow-through cell (FT), and disintegration (DI) tests. The determination of hydrodynamic flow was based on the dissolution rate of United States Pharmacopeial salicylic acid nondisintegrating calibrators, and showed that, compared with the PD and RB methods, the FT method produced a lower hydrodynamic flow value whereas the DI method produced a higher value. The hydrodynamic flows during the PD and RB tests appeared to be similar at the same rotational speed, although the flow patterns around the tablet differed; with the RB method, homogeneous dissolution occurred from all surfaces of the tablet, while with the PD method, dissolution from the lower surface was slower. The use of a sinker seemed to enhance dissolution from the lower surface. Such differences in hydrodynamic flow could explain the apparently different dissolution behaviors of disintegrating prednisone and nondisintegrating acetaminophen tablets when assessed by the PD and RB methods. These differences in hydrodynamic flow between in vitro tests should be considered when choosing dissolution tests for studying in vitro/in vivo relationships and for quality control purposes.

Assessment of gastric acidity of Japanese subjects over the last 15 years.

The gastric acidity of young to elderly Japanese subjects from 1989 to 1999 was assessed and compared with that obtained in 1984, using GA-Test capsules containing acid-dissolving granules of riboflavin. The percentage of achlorhydric subjects increased with age as observed before, however, an over all decrease in all age categories year by year was noted. The percentage of achlorhydric subjects aged 50 years in 1995-1999 was about 40%, which was lower than that (60%) in 1984. However, such a chronological change was not observed when the percentage of achlorhydric subjects was determined according to birth year, indicating that it is related to the birth year of subjects. The percentage of achlorhydric subjects correlated with infection by Helicobacter pylori. Considering the high percentage of achlorhydric elderly, bioavailability and bioequivalence studies should be performed taking into consideration the effects of gastric acidity on the in vivo performance of drug products.

Serum biomarker-based validation of a self-administered diet history questionnaire for Japanese subjects.

Although several self-administered dietary assessment questionnaires have been developed for Japanese subjects, they have seldom been validated with objective measures. We validated a recently developed self-administered diet history questionnaire (DHQ) with fatty acids in serum phospholipid fractions, alpha- and beta-carotenes and alpha-tocopherol in serum as a gold standard using 86 university workers (42 men and 44 women, age-range=24-67 y). The age-adjusted Pearson partial correlation coefficients between the intakes of marine origin n-3 polyunsaturated fatty acids (PUFA) (crude values, energy-adjusted values by residual method, energy density, and fat density) and the serum phospholipid concentrations (percentage of total fatty acids) were 0.49, 0.51, 0.52, 0.48, and 0.58, 0.69. 0.66, 0.69 in men and women respectively. The correlation coefficients between intakes (microg/d) and the corresponding serum concentrations (micromol/L) were 0.43 and 0.40 in men and 0.42 and 0.60 in women for alpha- and beta-carotene respectively. It was -0.23 in men and -0.22 in women for alpha-tocopherol. The intakes of major foods (g/d) of marine origin n-3 PUFA, alpha- and beta-carotenes showed a relatively high level of correlation with the corresponding serum concentrations, whereas the level was generally lower than those observed in the analysis with the nutrient intakes. The results suggest that DHQ ranks individual adequately for marine origin n-3 PUFA, alpha- and beta-carotene intakes.