Formulation and stability of rofecoxib suppositories

Rofecoxib (ROF) is an analgesic, antipyretic and anti-inflammatory drug. ROF is available only in the form of tablets and oral suspension on the Egyptian market. Suppositories were formulated as a new dosage form to avoid its extensive metabolism in the liver and decrease its gastrointestinal effects especially for patients suffering from gastrointestinal disorders. In this study different suppository bases were used, water-soluble base mixtures of polyethylene glycols as well as lipophilic bases which include cocoa butter, Witepsol E75, Suppocire AM and Suppocire CM. The prepared formulae were examined for their drug content, weight uniformity, melting range, disintegration time, fracture point and in vitro release. The effect of different types and concentrations of non-ionic surfactants, namely Polysorbate 80, Brij 58 or Myrj 52, on the release characteristics of the drug from selected fatty suppository bases was also investigated. Co-grinding of the drug with either PVP 40000 or Avicel pH 101 at 1:5 w/w ratio was also incorporated in selected fatty suppository bases in order to investigate their role in enhancement of the drug release. Stability study was also performed in the prepared suppositories using HPLC technique. Moreover, the anti-inflammatory activity was studied in rats using paw-edema method and the results were investigated by statistical analysis using ANOVA test at the level of significance (P = 0.05). The prepared ROF suppositories were stable for two years and show superior anti-inflammatory activity in comparison with another anti-cox-2 inhibitor.