I have this same problem, though minor as they don't come too often and don't outstay their welcome, but they don't call ahead (I understand, they are family and of the generation that would expect to 'just pop in')
I also think that the husband might find this a bit of a respite if his unwell wife is getting on his nerves - this is very common with mental health issues of course!
I don't think you need to lie outright.
Every so often I say 'I'm so sorry, you've just caught me with [something] I need to finish before we go out'. I make the 'something' a form I have to fill in and get in the post, a computer issue I need to solve, or something they can't come and natter through.
If she happens to say later 'Did you get your form / issue sorted?' and you look blank for a moment, follow it up with 'Oh, it wasn't that major in the end, you just caught me right in the middle of sorting it'.
I also think they are unlikely to watch and see if you do actually go out!
I'd also say that if they do pick up that you are 'finessing the truth' then they may realise there is a problem.
I also agree that jumping ahead and making a time for them to call may be helpful.
I also think you have to work out how much you feel obligated because they are friends, and how much because she is unwell and they need support.
Morecambe and Wise - the lost tape
Coward that I am.