Dissolution and pharmacokinetic studies on controlled release indomethacin suppository
Zhang, Y.H.; Liu, G.H.; Ping, Q.N.
Yao Xue Xue Bao 22(8): 580-585
1987
ISSN/ISBN: 0513-4870 PMID: 3450161 Document Number: 297053
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 constant was found to be 11.37%/h (t .ltoreq. 8 h); 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 (Ka0 = 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.