Development of tramadol hydrochloride rectal gel preparations and evaluation of analgesic activity in experimental animals

Tramadol rectal gel preparations were developed using poloxamer or hydroxyethylcellulose as a gel base. The tramadol rectal gel using poloxamer has a gel point at 36 °C and was more bioadhesive (65.5 ± 2.4 x 10 2 dyne/cm 2 ) to the rectal mucous membrane than was the gel with the hydroxyethylcellulose base (37.4 ± 2.2 x 10 2 dyne/cm 2 ) with the gel strength of 87 ± 2 and 70 ± 2 s, respectively. All rectal gel formulations were colorless, clear, viscous liquid with a pH range of 6.65-7.13. In an in vitro release study, the release profiles of the drug from both rectal gels were similar and the cumulative amount of drug release was about 97 and 98 % in 5 h for the mucoadhesive gel and thermoreversible gel, respectively. Analysis of the release kinetics revealed that the drug might be released from the rectal gels by non-Fickian diffusion. In an in vivo analgesic study, administration of tramadol (0.25, 0.5, and 1.0 mg) rectal gel using poloxamer as the gel base, exerted a marked increase in the latency of the nociceptive response in mice. Similar results were also observed when using hydroxyethylcellulose as the base. These results indicated that tramadol rectal gels prepared using poloxamer or hydroxyethylcellulose as a gel base showed a complete release of the drug from the bases, as well as prolonging the latency of a nociceptive response in experimental animals.