I am running windows vista, and any drives in my computer while running defraggler cannot be removed by ejecting or safely removing because they are in use. This I would assume to be caused by defraggler constantly monitoring space on all drives even if they are not being defraged.
Although closing defraggler will allow you to eject the disc, this is not possible to do when a defrag is in process.
This could be fixed by allowing discs to be 'ejected' from defraggler and/or stopping monitoring on all drives that are not being defraged.