錠剤からの薬物溶出挙動に対する種々の崩壊剤の添加効果

抄録

The paddle rotation speed of 50 rpm has widely been accepted for dissolution tests since the implementation of Guidelines for Bioequivalence Studies in Japan. However, there have been a limited number of systematic studies reporting the effect of disintegrants on drug dissolution evaluated at 50 rpm. In this study, we compared the effect of three disintegrants, croscarmellose sodium (CCS), carboxymethylcellulose (CMC) and cros povidone (CP), on the disintegration and dissolution rates of ethenzamide, a poorly water soluble model drug, from tablets. The disintegrants were formulated in the tablets so that more than 85% of the drug would be dissolved in 30 to 60 min by the dissolution test at 50 rpm. It is worthwhile examining the effect of disintegrants on the tablets with such a dissolution rate because it is generally recognized that it is not easy to prepare a tablet bioequivalent to a standard tablet with such a dissolution rate. CCS and CMC increased the dissolution rate at a content of 1% or less. CP showed no effect as a disintegrant at this content due to interaction with magnesium stearate. However, its effect on the dissolution rate was the largest among the three disintegrants at the concentration of more than 1%. The increase in dissolution rate was well correlated with increase in the water absorption rate by the tablets with disintegrants.