Pharmaceutical Evaluation of Hollow Type Suppository. II. Indomethacin Added Form and Release Characteristics of Hollow Type Suppository

Abstract

The hollow cavities of suppositories made from oily-base material (Witepsol H-15) were filled with indomethacin (IDM) in the following 4 forms: IDM fine powder (I]; IDM physically mixed powder with lactose (II); IDM in propylene glycol (PG) suspension (III); and IDM in macrogol 300 solution (IV). The dissolution percentage of IDM and their releasing aspects were observed in vitro. By using I, after melting the base material of hollow type suppository, the released powder did not become wet easily and was difficult to diffuse into the solution. IDM dissolved into the solution very slightly. By the use of II, IDM mixture powder dissolved into the aqueous solution a little faster than that by the case I, but no considerable improvement could be found. The difficulty in wetting was improved in III, but the dissolution was not perfect. In the case of IV, IDM dissolved more quickly and almost completely. Plasma concentration of IDM was measured in rabbits after the rectal administration of the suppositories including 50 mg of IDM in 2 kinds of hollow types, one of which had fine power (I) and the other included macrogol 300 solution (IV) and 2 kinds of conventional types one prepared from oily-base material (V) and the other made of water soluble base material (IV), with IDM. The hollow type suppository was apparently superior to the conventional one made of the same kind of oily-base material. Compared to the conventional type suppository made of water soluble base material (VI), the hollow type one including macrogol 300 solution (IV) could be expected to have an immediate effect, because its tmax [time to reach maximum concentration] was smaller than VI.