Try to avoid ambiguities at, or near, the 3' end of the primer and when calculating the annealing temperature treat all degenerate bases as A or T not as G or C to ensure that all primer sequences can anneal if their complimentary sequences exist. Design your primers in regions which have the smallest number of degenerate bases even if it means that primer design is not ideal. Remember that you can never sequence anything except the primer sequence under a primer so if the degeneracies are useful to your analysis then move the primer further out.