Influence of phystcochemical interactions on the properties of suppositories IV. Factors influencing the in vivo release of ketoprofen and metronidazole from fatty suppository bases

Abstract

The advantages and disadvantages of animal models employed for the testing of suppositories in vivo are discussed and the rat has been selected for the present work. Some of the important variables involved in these tests have been investigated using fatty suppositories consisting of binary mixtures of pure mono-acid triglycerides. The drugs employed, ketoprofen and metronidazole, give solution and suspension suppositories, respectively. Using Kendall's method of rank correlation, the bioavailability of ketoprofen or metronidazole has been found to correlate significantly with the rate of spreading of fatty suppositories but not with the plastic viscosity of the base, determined in a rotational viscometer. Accurate prediction of the plots of drug plasma levels vs time from individual mean data points from a number of rats is found to be difficult as reflected by the wide 95% confidence limits. The main use of such plots is to indicate trends. The highest blood level profiles for both the solution and suspension suppositories are found to be given by formulations containing the binary triglyceride mixture consisting of 60% w/w tricaprin and 40% w/w trilaurin as constituents of the base.