PREPARATION AND IN-VITRO EVALUATION OF KETOTIFEN FUMARATE AS RECTAL SUPPOSITORIES

Ketotifen Fumarate (KF) is an antihistamine with sedating effect that also has a stabilizing action on mast cell. It is used in the treatment of allergic conditions, and prophylactic management of asthma. The objective of this study was to prepare KF as suppository as an attempt to increase the bioavailability by avoiding the hepatic first pass metabolism. twelve formulas were prepared (ten conventional and two hollow) using fusion method and by using different bases such as polyethylene glycols of different (grades and ratios) and semisynthetic glyceride (SSG) as fatty base. The prepared suppositories were evaluated for physical properties such as weight variation, content uniformity softening time, melting time and hardness. Invitro release profiles were also evaluated .The effect of the type of the base, the grade and ratio of PEGs mixture where evaluated. The effect of temperature and time of storage on the physical properties and the release profile of the suppository were studied. All of the prepared suppositories had acceptable physical properties and the maximum release of ketotifen (100%, 99%) was found from the F1 of PEGs 400:4000 (70:30) and F5 of PEGs 400:6000(70:30), respectively as a conventional suppositories. The release of drug from fatty based suppositories (SSG) was (51%). It enhanced by adding non-ionic surfactant (tween80) to reach 75%. The hollow suppositories F11 and F12 have faster release profile than the conventional one .Formulas F1 and F5 as conventional type suppositories and F11 as hollow type suppository were considered the good and suitable formulas because they exhibited a good physical properties with higher drug release. However, F1 was selected as the best one because it had excellent physical properties with highest % of KF release.