APPLICATION OF SUCROSE LAURATE, A NEW PHARMACEUTICAL EXCIPIENT, IN PERORAL FORMULATIONS OF CYCLOSPORINE-A

Membrane permeability of sucrose laurate was studied using a regenerat ed cellulose acetate membrane with an M(w) cutoff of 5000. Both the su crose laurate micelle and even the sucrose laurate monomer were unable to cross the artificial membrane. Sucrose laurate, however, was found to enhance the in vitro absorption of cyclosporin A when normal epith elial tissue and Peyer's patch tissue of guinea pigs were used. Compar ed to the commercially available drinking solution, absorption was rai sed by a factor 10. Excess amount of surfactant reduced cyclosporin A absorption. Despite the large excess of sucrose laurate (50 x ), the a bsorption of cyclosporin A was still superior to the drinking solution . Choleic acid was also found to raise absorption by a factor of 5-6. A comparison of the absorption between normal epithelial and Peyer's p atch tissues indicated that the absorption by endocytosis does not con tribute significantly to the overall absorption of cyclosporin A. Rega rding the high degree of absorption, sucrose laurate may be considered as a new promising excipient for peroral formulations. Preliminary fo rmulation experiments showed that a solid peroral dosage form of cyclo sporin A could be made, using sucrose laurate as an excipient. However , further optimization studies must be performed in order to obtain a preparation suited for human application.