DISSOLUTION AND PHARMACOKINETIC STUDIES ON CONTROLLED RELEASE INDOMETHACIN SUPPOSITORY

This paper deals with the evaluation of a controlled release indomethacin suppository (CRIS) by in vitro and in vivo tests. The dissolution test was carried out by a basket method. Serum levels of indomethacin after rectal administration of CRIS and a conventional indomethacin suppository (CIS) in 6 human subjects were determined by a fluorescence spectrophotometry method. The pharmacokinetic parameters were fitted by non-linear least square method with Radio Shack TRS-80 micro-computer system. The dissolution test showed that the release-mechanism of CRIS in vitro may be described by apparent zero-order kinetics. The dissolution rate costant was found to be 11.37%/h (t≤8h); The results of in vivo test showed a desirable release behaviour of CRIS in human subjects. In other words, CRIS demonstrated a smoother serum concentration-time profile than CIS in elimination phase but much lower in maximum concentration following a single dose(75 mg). The rate of absorption of CRIS in human was found to conform to apparent zero-order kinetics (K_a,⁰=9.60%/h) during the first 8 h, and there is a linear relationship between percent absorption in vivo and percent dissolution in vitro (r=0.9979, p<0.001). Bioavailability of CRIS is also better than that of CIS.