Release of pyrazolone derivatives from suppositories formulated with hydrophilic and hydrophobic bases.
The release and dissolution of aminophenazone and propyphenazone from suppositories prepared with Witepsol (H 15 and S 55), Suppocire (BM and AS 2), and macrogols 400 and 4000 placed in a small volume of water enclosed within a semipermeable wall, were followed by measuring the concentrations of dissolved drug that crossed the wall into an outside aqueous compartment. The rates of appearance of drugs in the outside compartment depended on their "affinities" to the bases, ascertained by determining the lipid/water partition coefficients. Propyphenazone had more "affinity" to less hydrophobic bases and was more slowly liberated from these; the opposite is true for aminophenazone. A higher proportion of mono- and diglycerides in Witepsol S 55 and Suppocire AS 2 influences the solubility of propyphenazone which was thereby liberated more easily than from Witepsol H 15 and Suppocire BM. The presence of polyethylene glycols in an aqueous solvent increased the solubilities of both drugs. On the other hand, marked solubilities in the bases cause slower liberation. With the macrogols, mixtures with a larger proportion of higher-molecular components turned out as better bases for propyphenazone suppositories, those with a smaller proportion of these components were more suitable for aminophenazone suppositories.
D000632:Aminopyrine / Q000008:administration & dosage / Q000378:metabolism*; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D013488:Suppositories
D013488:Suppositories; D000632:Aminopyrine; C009077:propyphenazone; D000983:Antipyrine