The effect of polysorbate 80 on the rectal absorption of carbamazepine from a fatty suppository was investigated in the rabbit. Each animal received successively (with a wash-out of 1 week between every administration) two oral capsules of 100 mg, a suppository of carbamazepine 200 mg without surfactant, and a suppository of carbamazepine 200 mg including 2% polysorbate 80. After oral administration, the following values were obtained: Cmax 43 ± 17 μmol/l; Tmax, 5.1 ± 2.3 h; AUC, 391 ± 204 μmol h l−1. Subsequent to rectal administration of a suppository without polysorbate 80, the corresponding values were: Cmax, 28 ± 2.9 μmol/l; Tmax, 2.8 ± 1.3 h; AUC, 203 ± 29 μmol h l−1. The inclusion of polysorbate 80 resulted in a Cmax of 26 ± 6.2 μmol/l at 1.7 ± 0.5 h. The AUC value amounted to 242 ± 66 μmol h l−1. In the rabbit, rectal administration of carbamazepine from a suppository is more regular than oral absorption from capsules. Polysorbate 80 could enhance the rate and reproducibility of rectal absorption of carbamazepine from a fatty suppository: the serum concentration at 45 min amounted to 20.9 ± 3.8 μmol/l for the suppository containing polysorbate 80 vs 14.6 ± 5.9 μmol/l for that without.

The effect of surfactants on physicochemical properties and on the release characteristics of carbamazepine from fatty suppositories was investigated in vitro. Four surfactants, polyoxyethylene 50-stearate (Simulsol M(R)), polyoxyethylene 23-lauryl ether (Brij 35R), polysorbates 20 and 80, were examined as adjuvants. The dissolution rate was enhanced by all surfactants used. The dissolution rate at 30 min increased from 54% without surfactant, to 100% with polysorbate 80 (2%). The liquefaction time could be the limiting factor for the dissolution rate of carbamazepine. The better solubilising effect of polysorbate 80 can be due to the better incorporation capacity of its micellae.