From vague memory, I'm not sure Frank Zappa lost his way, but actually found what he'd been looking for the whole time. Prior to the Synclavier he was forced to use humans to bring his compositions to life, and therefore his compositions were written with this in mind; a forced compromise of sorts.
Can't be too upset though given his prolific album releases prior to his Synclavier moment.
You're right, he was such a misanthrope that he didn't enjoy working with musicians, yet, he worked with so many brilliant musicians that made his work great.
I think of his albums where he heavily overdubbed concert footage, probably peaking in The Man From Utopia which just sounds like the greatest concert you never went to.
Also worth remembering that his most synclavier-heavy work came as he was dying of cancer. And also that the "synclavier phase" is like 4-5 albums out of over 60.
Can't be too upset though given his prolific album releases prior to his Synclavier moment.