The preparation and evaluation of a tablet dosage form of cyclosporine in dogs.

Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct compression was then selected for comparison with the commercial oil solution placed into soft gelatin capsules. The study involved a randomized crossover design in six dogs. In order to determine absolute bioavailability and to compensate for any time-dependent changes in clearance, an intravenous tracer dose of 3H-CsA was administered along with each oral test product on each of two occasions. Absolute bioavailability (mean +/- SD) was 46.0 +/- 11.1 and 45.4 +/- 9.9% for the capsules and tablets, respectively. Cmax, tmax, and mean absorption time were not significantly different between the two products. No differences were observed in the pharmacokinetics of the intravenously administered CsA in the two experiments, which were separated by 8-13 days. We conclude that the proposed tablet formulation for CsA is equivalent in dogs to the commercial dosage form placed into soft gelatin capsules.