• M A Salman, A Sahin, M A Onur, K Oge, A Kassab, and U Aypar.
• Hacettepe University Faculty of Medicine, Department of Anaesthesiology and Reanimation, Ankara, Turkey. asalman@hacettepe.edu.tr
• Acta Anaesthesiol Scand. 2003 Sep 1; 47 (8): 1006-12.

BackgroundControlled release techniques are used to increase the duration of action and decrease the toxicity of drugs. Any controlled release form of tramadol in spinal or epidural blocks has not been studied previously. Tramadol was encapsulated into polyhydroxybutyrate (PHB) microspheres and release kinetics was studied. The epidural analgesic effect of this solution in rats was also compared with free tramadol.MethodsControlled release of tramadol from PHB microspheres into 10 ml of phosphate buffer solution at pH 7.4 and 37 degrees C was studied in vitro. In vivo studies were performed in 40 rats. Epidural catheters were placed during general anaesthesia. Rats were randomly allocated into one of the four study groups to receive normal saline, 4 mg of tramadol, PHB microspheres without tramadol, or 4 mg of tramadol encapsulated into PHB microspheres. Analgesia was evaluated with tail flick tests performed at 52.5 +/- 0.5 degrees C before injection and at intervals up to 30 h after injection. Catalepsy and loss of corneal reflexes were considered as signs of supraspinal toxicity.ResultsIn vitro drug release was observed for more than 6 days. Epidural analgesic effects of tramadol released from PHB microspheres were observed for 21 h, whereas an equal dose of free tramadol was effective for less than 5 h. No signs of toxicity were observed.ConclusionControlled release of tramadol from PHB microspheres is possible, and pain relief during epidural analgesia is prolonged by this drug formulation compared with free tramadol.

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