Evaluation of emulsifiable glasses for the oral administration of cyclosporin in beagle dogs

Abstract

Solid state emulsifiable glasses have been proposed as delivery systems for poorly water soluble drugs. This study assessed the utility of the emulsifiable glass (EG) technology for the oral delivery of cyclosporin. EG formulations were prepared, evaluated in vitro, and the bioavailability assessed in beagle dogs. Although the standard EG formulations (i.e. containing no surfactant) produced a dispersed phase upon reconstitution, significant quantities of residual oil were present within these systems. The absolute bioavailability of cyclosporin after administration of an EG cyclosporin formulation (12.5 mg dose) was compared with a 25 mg Sandimmun® capsule and a 25 mg surfactant-based self-emulsifying lipid formulation (SEDDS) in a randomized crossover study conducted in four beagle dogs. The absolute bioavailability and the major pharmacokinetic parameters of cyclosporin were similar for the three oral formulations. Subsequently, a surfactant enhanced emulsifiable glass (SEEG) was formulated which offered the following advantages over the standard EG systems: (i) rapid, efficient and complete emulsification, (ii) a four-fold increase in drug loading capacity, and (iii) a two-fold decrease in processing time. The relative bioavailability and pharmacokinetic characteristics of the SEEG formulation were evaluated: relative to Sandimmun® in a two-way crossover in four beagle dogs. There were no significant differences in either the major pharmacokinetic parameters or the relative bioavailability of the two formulations. Comparing the two studies, there was significantly less variability in the blood cyclosporin profiles after administration of the SEEG formulation than after administration of the standard EG formulation. These studies demonstrate the utility of EG technology for the oral delivery of cyclosporin, and develop the technology to include surfactant enhanced systems which offer improved characteristics.