الفهرس 
General introductionOnly 14 pages are availabe for public view
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Abstract
The work in this investigation involves a pharmaceutical study on the formulation and evaluation of mucoadhesive liquid suppositories containing certain hepatotoxic drugs as a way to reduce drug-induced hepatotoxicity. Liquid suppositories were prepared using thermoreversible poloxamers (P407and P188) The work includes the preparation of diclofenac sodium liquid and conventional suppositories. The physicochemical parameters (gelation temperature, gel strength and mucoadhesive force) and dissolution of the prepared suppositories were studied. Different sodium salts and tweens were incorporated and their effects on physicochemical parameters were studied. The bioavailability of the drug from liquid suppositories was studied and compared to that of conventional suppositories in rabbits by High Performance Liquid Chromatographic technique. The effect of the drug on the liver and rectum was histologically studied in rabbits. Also, the work in this thesis includes the formulation and evaluation of ketorolac tromethamine liquid and conventional suppositories. Different mucoadhesive polymers were incorporated and their effect on the physicochemical parameters and dissolution were investigated. The effect of the drug on the gastrointestinal tract was studied by histological examination of stomach, duodenum and rectum of rabbits. While, the effect of the drug on the liver was studied by means of biochemical assay of liver marker enzymes in addition to histological study of liver tissues in rabbits. The obtained results revealed that diclofenac sodium and ketorolac tromethamine can be formulated in mucoadhesive thermoreversible poloxamer-based liquid suppository forms. The prepared suppositories exhibited adequate physicochemical and dissolution properties. In addition, liquid suppositories exhibited higher drug bioavailability than conventional suppositories. After administration of the prepared liquid suppositories, no harm was produced to rabbit liver and gastrointestinal tract. Based on the results of this study, it could be concluded that poloxamer-based liquid suppositories containing a hepatotoxic drug are considered a safe and effective rectal delivery system with reduced hepatotoxic effect.