Formulation and evaluation of novel mucoadhesive ketorolac tromethamine liquid suppository

Abstract

Ketorolac tromethamine (KT) loaded mucoadhesive liquid suppository was prepared as a site-specific mucoadhesive
rectal dosage form. Poloxamer mixture formed of 21% P407 and 9% P188 were used as liquid suppository base. Invitro 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.