Influence of storage temperature on indomethacin release from fatty-base suppositories in vitro and in vivo.
The release of indomethacin from fatty-base suppositories, which had been stored at a low (4 degrees C) and a high (25-30 degrees C) temperature for about one month, was examined in vitro and in vivo. In the in vivo experiments, the plasma indomethacin levels after administration of suppositories stored at different temperatures were measured in conscious and anesthetized rats. In the in vitro release test using a dialysis cell method, much lower amounts of indomethacin were released from the suppositories stored at a high temperature than from those stored at a low temperature. The melting point of suppositories stored at a high temperature was higher by approximately 2 degrees C than those stored at a low temperature. In conscious rats, the plasma indomethacin levels attained after the intrarectal administration of suppositories stored at a high temperature were slightly lower than those after the animals were given suppositories stored at a low temperature, but the difference was significant only 30 min after administration. In anesthetized rats, the plasma indomethacin levels were markedly lower than those in conscious rats, and the influence of the storage temperature on the plasma indomethacin levels was clearly observed. These results suggest that in conscious rats many factors such as a locomotor hyperactivity and enhancement of gastrointestinal motility caused by the rectal administration mask the real character of suppositories. The in vitro and in vivo results show that the release of indomethacin from fatty-base suppositories stored at a high temperature is less than the release from those stored at a low temperature.
Yoshida
T
T
Department of Pharmacology, Okayama University Medical School, Japan.
Itoh
Y
Y
Gomita
Y
Y
Oishi
R
R
D000818:Animals; D004356:Drug Storage; D007213:Indomethacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D014677:Pharmaceutical Vehicles; D051381:Rats; D011919:Rats, Inbred Strains; D013488:Suppositories; D013696:Temperature; D014280:Triglycerides
D014677:Pharmaceutical Vehicles; D013488:Suppositories; D014280:Triglycerides; C009683:witepsol; D007213:Indomethacin