The influences of both the mixing ratios of Witepsol as a lipophilic base and the temperature on the drug release from the zonisamide suppositories was investigated. Mixed types of zonisamide suppositories consisting of Witepsol H-15 (H) and Witepsol S-55 (S) as a lipophilic base were prepared and the release of zonisamide from a suppository was determined using the dissolution apparatus in Paddle method of JPX III. The release rate of zonisamide from the Witepsol (H: S=4: 1) suppository and Witepsol (H: S=3: 1) suppository at 4 hours after start of the release test were 66.6% and 56.5%, respectively. The former was significantly higher (p<0.05) than that of the latter. The release volume and mean dissolution time (MDT) of zonisamide from a suppository increased and decreased, respectively, according to the high mixing ratio of Witepsol H 15.
The effect of low temperature (32 and 34°C) on drug release from the zonisamide suppositories was also studied using artificial membranes. The drug release properties were changed according to the mixing ratios of the two lipophilic bases and the temperature of the fluid tested. At a low temperature, the amount of released zonisamide correlated with the ratio of Witepsol S 55 in the suppository. However, the amount of the drug released from the zonisamide suppositories decreased at temperatures lower than normal body temperature. These results indicate that the ratio of Witepsol H 15 and Witepsol S 55 in suppositories was important while the temperature also influence drug absorption from the rectum with zonisamide suppositories.
