Formulation and evaluation of novel mucoadhesive ketorolac tromethamine liquid suppository

Ketorolac tromethamine (KT) loaded mucoadhesive liquid suppository was prepared as a site-specific mucoadhesive rectal dosage form. Poloxamer mixture formed of 21P407 and 9P188 were used as liquid suppository base. In-vitro release rate of KT from liquid suppository was studied and compared to that from conventional suppository. The safety of the prepared suppository on GIT was conducted; hepatotoxicity of KT after 5 days of administration of liquid suppository was evaluated histologically and biochemically. The levels of liver enzymes alanine aminotransferase (ALT); aspartate amino transferase (AST); alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were used as the biochemical markers of liver damage. The results obtained revealed that the addition of KT increased the gelation temperature of poloxamer gel and reduced the gel strength and the mucoadhesive force. The study of the release rate of KT from liquid suppository was significantly higher than from conventional suppositories. Histological pictures of the GI tissues indicated no pathological damage after 5 days of rectal administration compared to oral administration. Also; it was revealed that no hepato-cellular damage occurred after administration of liquid suppository; unlike oral administration; which produced certain hepato-toxicity. The administration of KT liquid suppository did not significantly increase the basic levels of ALT and AST when compared to the control. On the other hand; the administration of KT oral solution in a dose of 10 mg/kg body weight/day for 5 days significantly increased serum ALT and AST levels; thus; KT liquid suppository in poloxamer gel was a convenient; safe and effective rectal dosage form for administration with lower hepato-toxic effect

Physical and release properties of metronidazole suppositories

Purpose: A study was made of the effects of some bases and adjuvants on the physical and release properties of metronidazole suppositories with a view to providing more information for the optimization of the rectal formulation of metronidazole. Method: Suppositories (1g) containing 200mg of metronidazole each were prepared in witepsol (H15 and E75) and polyethylene glycol (PEG 2850 and 4650) bases; using different concentrations of Tween 80; sodium salicylate and methylcellulose as adjuvants. The setting time; solidification point and melting range of the suppositories were determined; along with their crushing strength; disintegration time and the time for 80of metronidazole to be released from the suppositories (t80). Results: The ranking of setting time for the suppositories was witepsol H15 PEG 2850 witepsol E75 PEG 4650; while the ranking of solidification point; melting range; crushing strength; disintegration time and the time for 80of metronidazole to be released from the suppositories (t80) was the reverse of that for setting time. Optimal concentrations of Tween 80 and sodium salicylate were observed for the suppository formulations. Using Kitazawa plots; all formulations showed two dissolution rate constants; k1 and k2 intersecting at time t1; with formulations containing 5 to 20w/w of methylcellulose exhibiting a third dissolution rate constant; k3 intersecting with k2 at time t2. Conclusion: The physical and release properties of metronidazole sup-positories are influenced considerably by the bases and adjuvants employed. Tween 80 and sodium salicylate can probably be used to formulate only immediate-release supposi- tories while methylcellulose can be useful for sustained-release metronidazole suppositories. Some insight into these inferences can be obtained from parameters derived from Kitazawa plots